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Commensal bacteria at the interface of host metabolism and the immune system Jonathan R Brestoff & David Artis AffiliationsCorresponding author Nature Immunology 14, 676–684 (2013) doi:10.1038/ni.2640 Received 19 March 2013 Accepted 10 May 2013 Published online 18 June 2013 The mammalian gastrointestinal tract, the site of digestion and nutrient absorption, harbors trillions of beneficial commensal microbes from all three domains of life. Commensal bacteria, in particular, are key participants in the digestion of food, and are responsible for the extraction and synthesis of nutrients and other metabolites that are essential for the maintenance of mammalian health. Many of these nutrients and metabolites derived from commensal bacteria have been implicated in the development, homeostasis and function of the immune system, suggesting that commensal bacteria may influence host immunity via nutrient- and metabolite-dependent mechanisms. 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The role of the immune system in governing host-microbe interactions in the intestine Eric M Brown, Manish Sadarangani & B Brett Finlay AffiliationsCorresponding author Nature Immunology 14, 660–667 (2013) doi:10.1038/ni.2611 Received 15 February 2013 Accepted 11 April 2013 Published online 18 June 2013 The mammalian intestinal tract harbors a diverse community of trillions of microorganisms, which have co-evolved with the host immune system for millions of years. Many of these microorganisms perform functions critical for host physiology, but the host must remain vigilant to control the microbial community so that the symbiotic nature of the relationship is maintained. To facilitate homeostasis, the immune system ensures that the diverse microbial load is tolerated and anatomically contained, while remaining responsive to microbial breaches and invasion. Although the microbiota is required for intestinal immune development, immune responses also regulate the structure and composition of the intestinal microbiota. Here we discuss recent advances in our understanding of these complex interactions and their implications for human health and disease. Xu, J. & Gordon, J.I. Honor thy symbionts. Proc. Natl. Acad. Sci. USA 100, 10452–10459 (2003). CASPubMedArticle Eckburg, P.B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005). This is the first comprehensive study to use a culture-independent approach to describe the composition of the intestinal microbiota in healthy adult humans. ADSISIPubMedArticle Ley, R.E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008). CASADSISIPubMedArticle Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012). 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Control of pathogens and pathobionts by the gut microbiota Nobuhiko Kamada, Grace Y Chen, Naohiro Inohara & Gabriel Núñez AffiliationsCorresponding author Nature Immunology 14, 685–690 (2013) doi:10.1038/ni.2608 Received 27 February 2013 Accepted 09 April 2013 Published online 18 June 2013 A dense resident microbial community in the gut, referred as the commensal microbiota, coevolved with the host and is essential for many host physiological processes that include enhancement of the intestinal epithelial barrier, development of the immune system and acquisition of nutrients. A major function of the microbiota is protection against colonization by pathogens and overgrowth of indigenous pathobionts that can result from the disruption of the healthy microbial community. The mechanisms that regulate the ability of the microbiota to restrain pathogen growth are complex and include competitive metabolic interactions, localization to intestinal niches and induction of host immune responses. 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Breck A Duerkop & Lora V Hooper AffiliationsCorresponding author Nature Immunology 14, 654–659 (2013) doi:10.1038/ni.2614 Received 18 February 2013 Accepted 16 April 2013 Published online 18 June 2013 The human body is colonized with a diverse resident microflora that includes viruses. Recent studies of metagenomes have begun to characterize the composition of the human 'virobiota' and its associated genes (the 'virome'), and have fostered the emerging field of host-virobiota interactions. In this Perspective, we explore how resident viruses interact with the immune system. We review recent findings that highlight the role of the immune system in shaping the composition of the virobiota and consider how resident viruses may impact host immunity. Finally, we discuss the implications of virobiota–immune system interactions for human health. Hooper, L.V., Littman, D.R. & Macpherson, A.J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012). CASADSPubMedArticle Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012). CASADSPubMedArticle White, D.W., Suzanne Beard, R. & Barton, E.S. Immune modulation during latent herpesvirus infection. Immunol. Rev. 245, 189–208 (2012). CASPubMedArticle Handley, S.A. et al. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell 151, 253–266 (2012). CASPubMedArticle Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010). CASADSISIPubMedArticle Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011). CASADSPubMedArticle Foulongne, V. et al. Human skin microbiota: high diversity of DNA viruses identified on the human skin by high throughput sequencing. PLoS ONE 7, e38499 (2012). CASADSPubMedArticle Zhang, T. et al. RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol. 4, e3 (2006). CASPubMedArticle Turnbaugh, P.J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009). CASADSISIPubMedArticle Pride, D.T. et al. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J. 6, 915–926 (2012). CASPubMedArticle Breitbart, M. et al. Viral diversity and dynamics in an infant gut. Res. Microbiol. 159, 367–373 (2008). CASISIPubMedArticle Weinbauer, M.G. Ecology of prokaryotic viruses. FEMS Microbiol. Rev. 28, 127–181 (2004). CASISIPubMedArticle DeMarini, D.M. & Lawrence, B.K. Prophage induction by DNA topoisomerase II poisons and reactive-oxygen species: role of DNA breaks. Mutat. Res. 267, 1–17 (1992). CASPubMedArticle Duerkop, B.A., Clements, C.V., Rollins, D., Rodrigues, J.L. & Hooper, L.V. A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc. Natl. Acad. Sci. USA 109, 17621–17626 (2012). ADSPubMedArticle Kim, M.S., Park, E.J., Roh, S.W. & Bae, J.W. Diversity and abundance of single-stranded DNA viruses in human feces. Appl. Environ. Microbiol. 77, 8062–8070 (2011). CASPubMedArticle Canchaya, C., Fournous, G., Chibani-Chennoufi, S., Dillmann, M.L. & Brussow, H. Phage as agents of lateral gene transfer. Curr. Opin. Microbiol. 6, 417–424 (2003). CASISIPubMedArticle Pride, D.T., Salzman, J. & Relman, D.A. Comparisons of clustered regularly interspaced short palindromic repeats and viromes in human saliva reveal bacterial adaptations to salivary viruses. Environ. Microbiol. 14, 2564–2576 (2012). CASPubMedArticle Ivanov, I.I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008). CASISIPubMedArticle Mazmanian, S.K., Liu, C.H., Tzianabos, A.O. & Kasper, D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005). CASISIPubMedArticle Kuss, S.K. et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334, 249–252 (2011). CASADSPubMedArticle Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. USA 108, 5354–5359 (2011). ADSPubMedArticle Kane, M. et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334, 245–249 (2011). CASADSPubMedArticle Schowalter, R.M., Pastrana, D.V., Pumphrey, K.A., Moyer, A.L. & Buck, C.B. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 7, 509–515 (2010). CASISIPubMedArticle Miller, C.S., Avdiushko, S.A., Kryscio, R.J., Danaher, R.J. & Jacob, R.J. Effect of prophylactic valacyclovir on the presence of human herpesvirus DNA in saliva of healthy individuals after dental treatment. J. Clin. Microbiol. 43, 2173–2180 (2005). CASPubMedArticle Lazarevic, V. et al. Analysis of the salivary microbiome using culture-independent techniques. J. Clin. Bioinforma. 2, 4 (2012). CASPubMedArticle Bogaert, D. et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS ONE 6, e17035 (2011). CASADSPubMedArticle Nokso-Koivisto, J., Kinnari, T.J., Lindahl, P., Hovi, T. & Pitkaranta, A. Human picornavirus and coronavirus RNA in nasopharynx of children without concurrent respiratory symptoms. J. Med. Virol. 66, 417–420 (2002). PubMedArticle Minot, S., Grunberg, S., Wu, G.D., Lewis, J.D. & Bushman, F.D. Hypervariable loci in the human gut virome. Proc. Natl. Acad. Sci. USA 109, 3962–3966 (2012). 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Characterization of the viral microbiome in patients with severe lower respiratory tract infections, using metagenomic sequencing. PLoS ONE 7, e30875 (2012). CASADSPubMedArticle Willner, D. et al. Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals. PLoS ONE 4, e7370 (2009). CASADSPubMedArticle Brandl, K. et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455, 804–807 (2008). CASADSISIPubMedArticle Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011). CASADSISIPubMedArticle Virgin, H.W., Wherry, E.J. & Ahmed, R. Redefining chronic viral infection. Cell 138, 30–50 (2009). CASISIPubMedArticle Barton, E.S. et al. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447, 326–329 (2007). CASADSISIPubMedArticle Zuniga, E.I., Liou, L.Y., Mack, L., Mendoza, M. & Oldstone, M.B. Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections. Cell Host Microbe 4, 374–386 (2008). CASISIPubMedArticle Inchley, C.J. & Howard, J.G. The immunogenicity of phagocytosed T4 bacteriophage: cell replacement studies with splenectomized and irradiated mice. Clin. Exp. Immunol. 5, 189–198 (1969). CASPubMed Nelson, J., Ormrod, D.J., Wilson, D. & Miller, T.E. Host immune status in uraemia III. Humoral response to selected antigens in the rat. Clin. Exp. Immunol. 42, 234–240 (1980). CASPubMed Gorski, A. et al. Bacteriophages and transplantation tolerance. Transplant. Proc. 38, 331–333 (2006). CASPubMedArticle Eriksson, F. et al. Tumor-specific bacteriophages induce tumor destruction through activation of tumor-associated macrophages. J. Immunol. 182, 3105–3111 (2009). CASPubMedArticle Mori, K., Kubo, T., Kibayashi, Y., Ohkuma, T. & Kaji, A. Anti-vaccinia virus effect of M13 bacteriophage DNA. Antiviral Res. 31, 79–86 (1996). CASPubMedArticle Abstract• References• Author information Hooper, L.V., Littman, D.R. & Macpherson, A.J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012). CASADSPubMedArticle Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012). CASADSPubMedArticle White, D.W., Suzanne Beard, R. & Barton, E.S. Immune modulation during latent herpesvirus infection. Immunol. Rev. 245, 189–208 (2012). CASPubMedArticle Handley, S.A. et al. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell 151, 253–266 (2012). CASPubMedArticle Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010). CASADSISIPubMedArticle Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011). CASADSPubMedArticle Foulongne, V. et al. Human skin microbiota: high diversity of DNA viruses identified on the human skin by high throughput sequencing. PLoS ONE 7, e38499 (2012). CASADSPubMedArticle Zhang, T. et al. RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol. 4, e3 (2006). CASPubMedArticle Turnbaugh, P.J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009). CASADSISIPubMedArticle Pride, D.T. et al. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J. 6, 915–926 (2012). CASPubMedArticle Breitbart, M. et al. Viral diversity and dynamics in an infant gut. Res. Microbiol. 159, 367–373 (2008). CASISIPubMedArticle Weinbauer, M.G. Ecology of prokaryotic viruses. FEMS Microbiol. Rev. 28, 127–181 (2004). CASISIPubMedArticle DeMarini, D.M. & Lawrence, B.K. Prophage induction by DNA topoisomerase II poisons and reactive-oxygen species: role of DNA breaks. Mutat. Res. 267, 1–17 (1992). CASPubMedArticle Duerkop, B.A., Clements, C.V., Rollins, D., Rodrigues, J.L. & Hooper, L.V. A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc. Natl. Acad. Sci. USA 109, 17621–17626 (2012). ADSPubMedArticle Kim, M.S., Park, E.J., Roh, S.W. & Bae, J.W. Diversity and abundance of single-stranded DNA viruses in human feces. Appl. Environ. Microbiol. 77, 8062–8070 (2011). CASPubMedArticle Canchaya, C., Fournous, G., Chibani-Chennoufi, S., Dillmann, M.L. & Brussow, H. Phage as agents of lateral gene transfer. Curr. Opin. Microbiol. 6, 417–424 (2003). CASISIPubMedArticle Pride, D.T., Salzman, J. & Relman, D.A. Comparisons of clustered regularly interspaced short palindromic repeats and viromes in human saliva reveal bacterial adaptations to salivary viruses. Environ. Microbiol. 14, 2564–2576 (2012). CASPubMedArticle Ivanov, I.I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008). CASISIPubMedArticle Mazmanian, S.K., Liu, C.H., Tzianabos, A.O. & Kasper, D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005). CASISIPubMedArticle Kuss, S.K. et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334, 249–252 (2011). CASADSPubMedArticle Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. USA 108, 5354–5359 (2011). ADSPubMedArticle Kane, M. et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334, 245–249 (2011). CASADSPubMedArticle Schowalter, R.M., Pastrana, D.V., Pumphrey, K.A., Moyer, A.L. & Buck, C.B. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 7, 509–515 (2010). CASISIPubMedArticle Miller, C.S., Avdiushko, S.A., Kryscio, R.J., Danaher, R.J. & Jacob, R.J. Effect of prophylactic valacyclovir on the presence of human herpesvirus DNA in saliva of healthy individuals after dental treatment. J. Clin. Microbiol. 43, 2173–2180 (2005). CASPubMedArticle Lazarevic, V. et al. Analysis of the salivary microbiome using culture-independent techniques. J. Clin. Bioinforma. 2, 4 (2012). CASPubMedArticle Bogaert, D. et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS ONE 6, e17035 (2011). CASADSPubMedArticle Nokso-Koivisto, J., Kinnari, T.J., Lindahl, P., Hovi, T. & Pitkaranta, A. Human picornavirus and coronavirus RNA in nasopharynx of children without concurrent respiratory symptoms. J. Med. Virol. 66, 417–420 (2002). 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10 juillet 2013 3 10 /07 /juillet /2013 06:44
Yasmine Belkaid & Shruti Naik AffiliationsCorresponding author Nature Immunology 14, 646–653 (2013) doi:10.1038/ni.2604 Received 05 February 2013 Accepted 02 April 2013 Published online 18 June 2013 The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective, we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology. Références Abstract• References• Author information Shklovskaya, E. et al. Langerhans cells are precommitted to immune tolerance induction. Proc. Natl. Acad. Sci. USA 108, 18049–18054 (2011). PubMedArticle Chu, C.C. et al. Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. J. Exp. Med. 209, 935–945 (2012). CASPubMedArticle Igyarto, B.Z. et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity 35, 260–272 (2011). CASISIPubMedArticle Scott, C.L., Aumeunier, A.M. & Mowat, A.M. 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10 juillet 2013 3 10 /07 /juillet /2013 06:40
The microbial communities that colonize living organisms are collectively referred to as the 'microbiota'. These resident commensals are well adapted to the ecological conditions of their host and constitute a complex ecosystem in which host-microbe, environment-microbe and microbe-microbe interactions dictate the composition and dynamics of the community. As with every ecosystem, commensal species occupy a niche, are evolutionarily adapted and continuously selected by the environmental pressures in the niche, and compete with other species for niche resources. In mammals, the gut microbiota has coevolved to provide essential functions for host physiological processes, such as the acquisition of nutrients, the development and maturation of the immune system and enhancement of the intestinal barrier. In this issue of Nature Immunology, we provide a series of specially commissioned articles to discuss recent advances on the understanding of the complex relationship between the microbiota and the host immune system (http://www.nature.com/ni/focus/microbiota). The gastrointestinal tract contains the most abundant commensal community in mammals. However, other anatomical sites are colonized by unique communities of bacteria, with their structure and composition determined by their unique environment. In their Perspective, Belkaid and Naik review the present understanding of the physiological impact of resident commensals in the skin as well as the oral, vaginal and airway mucosa. In contrast to the dominant role of the gut microbiota, which can control the development of the immune system and set systemic thresholds for immune activation, the microbiota at sites other than the gut has a more local and discrete influence on processes such as tissue homeostasis, immune responses and tissue repair. Whereas recent efforts have generated a wealth of information on the composition of host-associated bacterial communities, much less is known about the viruses that colonize healthy people (the so-called 'virobiota') or the effect of viral genes (the 'virome') on host immunity. Study of the virobiota is an emerging field, and understanding of virobiota–immune system interactions is very preliminary. In their Perspective, Duerkop and Hooper provide a framework for considering how resident viruses associated with either the bacterial commensals (phages) or the host cells can shape microbiota communities and influence host immunity. Four commissioned Reviews discuss the complex interactions between the gut microbiota and the immune system. Despite the beneficial aspects of microbial colonization of the intestine, the abundance and proximity of such microbes to the host epithelium poses a major challenge to host integrity. Finlay and colleagues review the strategies used by the immune system to confine the microbial community in the lumen of the intestinal tract and achieve homeostasis. These include physical and biochemical barriers (the mucus layer, secretion of antimicrobial peptides and immunoglobulin A), as well as continuous surveillance by cellular and molecular components of the innate and adaptive immune system. This Review also discusses how environmental triggers, such as dietary changes, gastrointestinal pathogens or antibiotic treatment, or host-related factors, such as genetic susceptibility or immunodeficiency, can lead to a breakdown in host-microbe mutualism. Chu and Mazmanian cover recent research on the symbiotic relationship between invertebrate or vertebrate hosts and their bacterial communities and suggest that pattern-recognition receptors may have evolved to mediate the bidirectional cross-talk between microbial symbionts and their hosts. From Hydra to humans, these authors provide examples that highlight the role of these receptors in mediating the recognition of commensals and shaping the composition of microbiota, as well as in inducing tolerance toward symbiotic bacteria through local and systemic responses. Finally, two Reviews discuss how various aspects of microbiota activity can influence host metabolism and immune function. Commensal bacteria regulate the production and bioavailability of diet-dependent nutrients and metabolites such as bile acids, short-chain fatty acids and vitamins. Brestoff and Artis discuss how such commensal-derived products modulate the development and function of the immune system in health and disease. The commensal microbiota also protects against colonization by pathogens. Nuñez and colleagues highlight several mechanisms by which such interactions take place, such as competitive metabolic interactions and colonization of intestinal niches. A question central to understanding the complex interactions between host and microbiota is how the immune system distinguishes between commensals and pathogens. All bacteria, tolerated or not, share the same molecular patterns and are sensed by the same recognition pathways and receptors. The common opinion presented in this Focus is that recognition of pathogens versus commensals is not 'hard-wired' in the host immune system. The process is instead one of education. Hosts learn to recognize, restrain and tolerate their bacterial commensals. Through birth, breastfeeding and social interactions, mammals inherit a preselected community of microbes that is able to integrate into the physiological and homeostatic requirements of its host. Both the microbiota and the host use tools and signals shaped by millions of years of coevolution to maintain a constant dialog and a mutualistic relationship. As with any relationship, things can go wrong. Small imbalances introduced by the host's genetic makeup and/or various triggers, such as recurrent immune responses or microbial dysbiosis, can over time disturb the dynamic equilibrium between host and commensals. In such circumstances, the microbiota can become an amplifier of pathological effects and can feed forward into deregulated pathways that lead to local or systemic disease. As this exciting area of research blossoms, it becomes more and more apparent that studies of the immune system during homeostasis or disease cannot ignore the microbial world within.
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3 juillet 2013 3 03 /07 /juillet /2013 09:52

New Tick-Borne Illness Could Be Worse Than Lyme Disease

Doctors May Not Even Know To Look For Borrelia Miyamotoi Infection

 

NEW YORK (CBSNewYork) — A new disease spread by deer ticks has already infected 100,000 New Yorkers since the state first started keeping track.

As CBS 2’s Dr. Max Gomez reported, the new deer tick-borne illness resembles Lyme disease, but is a different malady altogether – and it could be even worse.

The common deer tick is capable of spreading dangerous germs into the human bloodstream with its bite. However, Lyme disease is one of many diseases that ticks carry.

The latest disease is related to Lyme, and an infected person will suffer similar symptoms.

“Patients with this illness will develop, perhaps, fever, headache, flu-like symptoms, muscle pains — so they’ll have typical Lyme-like flu symptoms in the spring, summer, early fall,” said Dr. Brian Fallon of Columbia University. “But most of them will not develop the typical rash that you see with Lyme disease.”

Fallon, a renowned expert on Lyme disease at the New York Psychiatric Institute, said the importance of the new bacterium – called Borrelia miyamotoi — is that it might explain cases of what looked like chronic Lyme disease, but did not test positive for Lyme.

“The problem is that the diagnosis is going to be missed, because doctors aren’t going to think about Borrelia miyamotoi because they don’t know about it. 

And number two, if they test for Lyme disease, it will test negative, and the rash won’t be there,” Fallon said. 

“So they are not going to treat with the antibiotics, so the patient will have an infection staying in their system longer than it should.

While there is no test yet for the germ, the good news is that it appears the same antibiotic that kills Lyme disease also works – if it is given in the right doses and started early in the infection.

Remember, it takes a tick bite to get Lyme disease or the new bug, and the tick usually has to feed on your blood for at least 24 hours.

If you have been outdoors, have someone else do a full body check, Gomez advised. Ticks are small – only about the size of a sesame seed.

 

 

http://newyork.cbslocal.com/2013/07/02/new-tick-borne-illness-could-be-worse-than-lyme-disease/

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2 juillet 2013 2 02 /07 /juillet /2013 20:16
Ces dernières années ont été marquées par de nombreux progrès thérapeutiques dans la sclérose en plaques. Le fingolimod et le natalizumab ont actuellement pris une place importante dans le traitement de seconde ligne. Prochainement seront disponibles de nouvelles formes orales, le fumarate et le tériflunomide. Un autre anticorps monoclonal, l’alemtuzumab, spécifique d'une glycoprotéine située à la surface des lymphocytes (CD52) pourra être prochainement utilisé en seconde ligne. Cette avalanche thérapeutique pourrait se poursuivre car une étude publiée récemment dans Lancet suggère qu’un autre produit, le daclizumab, serait très efficace.
Les cliniciens sont d'autant plus chanceux que toutes ces molécules agissent sur des cibles immunitaires différentes. Ainsi, le daclizumab est un anticorps monoclonal humanisé spécifique du récepteur CD25 diminuant l’activation immunitaire via l’interleukine 2. Plus de 600 patients ont été inclus dans l'étude SELECT, randomisée, en double aveugle et contre placebo : 204 sous placebo, 208 sous daclizumab HYP 150 mg et 209 sous daclizumab HYP 300 mg. Le produit était injecté par voie sous-cutanée une fois toutes les quatre semaines et pendant 52 semaines. Les critères d’évaluation étaient tout à fait classiques pour ce type d'études.
Il a été observé une diminution du taux annualisé de poussées dans les deux groupes traités (réduction de 50 à 54 %), une réduction du nombre de lésions prenant le gadolinium, de nouvelles lésions en T2 et en T1. Le taux d'effets indésirables a été de 6 % dans le groupe placebo, 7 % dans le groupe traité par 150 mg et de 9 % dans le groupe 300 mg. Deux pour cent des patients ont eu des infections sérieuses. Un malade sous 150 mg de daclizumab est décédé d'un abcès du psoas. Quatre patients ont eu un cancer (2 mélanomes et un cancer du col dans le groupe traité et un cancer du col dans le groupe placebo).
Les auteurs concluent à l’efficacité du daclizumab. Ce traitement est cependant associé à une augmentation du risque d’infection et d’effets secondaires cutanés et hépatiques. D’après les auteurs, un monitoring étroit pourrait diminuer les conséquences de ces problèmes. On peut cependant regretter que cette étude soit conduite contre placebo chez des patients qui dans 75 % des cas n’avaient jamais eu de traitement de leur sclérose en plaques. Toutes les sociétés savantes et les cliniciens sont pourtant d’accord sur l’intérêt d’un traitement précoce par les molécules de référence que sont les interférons. Il existe des contraintes méthodologiques dans les phases de développement des médicaments mais le fait que la majorité des patients inclus proviennent de pays non européens suscite des interrogations éthiques.


Dr Christian Geny Publié le 02/07/2013


Ralf Goldet coll. for the SELECT study investigators. : Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet 2013; 381: 2167–75
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30 juin 2013 7 30 /06 /juin /2013 14:42
http://manuelanthony.wordpress.com/2012/03/04/la-flore-intestinale-des-enfants-autistes-est-differente-de-celle-des-enfants-non-autistes/ Des scientifiques ont découvert que les bactéries présentes dans l’intestin des enfants autistes sont différentes de celles des enfants non autistes. Des chercheurs de la Mailman School of Public Health de l’université Columbia [New York] ont découvert que les micro-organismes vivant dans les intestins des enfants autistes sont différents de ceux des autres enfants, mais ils n’ont pas encore réussit à déterminer si cette différence est la cause ou l’effet de l’autisme, a rapporté l’American Society for Microbiology [Association Américaine pour la Microbiologie]. Ces résultats, publiés dans la revue mBio, établissent qu’une bactérie appartenant au groupe des sutterellas de l’intestin apparaît dans 12 des 23 échantillons de tissu provenant d’enfants autistes. Cette bactérie n’était pas présente dans les échantillons des enfants non autistes. Selon Jorge Benoch, Président du département de microbiologie de l’université Stony Brook : "La bactérie Suturella a été associée à des maladies gastro-intestinales apparaissant après le diaphragme, par ailleurs il n’est pas encore évident qu’il s’agisse d’un agent pathogène ou non. Cette bactérie n’étant pas encore bien connue." Les scientifiques espèrent maintenant découvrir pourquoi ce micro-organisme n’est présent que chez les enfants autistes. "Les relations entre ces différents micro-organismes et l’hôte ainsi que l’évolution et le développement de la maladie représentent une problématique passionnante" explique Christine A. Biron professeure de sciences médicales à l’université Brown. "Cette publication est important car elle permet d’aborder la question de savoir comment les microbes peuvent influencer une maladie qui est encore mal comprise." ajoute le professeur Biron. L’étude a utilisé des échantillons de tissu provenant de l’intestin des enfants. Les scientifiques pensent que des résultats pourraient apporter une évolution positive en vue de trouver un lien direct entre les problèmes digestifs et les caractéristiques de comportement chez les enfants autistes. "La plupart des études qui ont établit un lien entre le microbiome intestinal et l’autisme ont été réalisées sur des échantillons de selles", explique Benach. "Mais les micro-organismes présents dans les selles ne représentent pas forcément les microbes qui se trouvent sur la paroi intestinale. Ce qui peut apparaître dans un échantillon de selles peut être différent de ce qui est directement incrusté dans les tissus." Georgina Gomez de la Cuesta, responsable de recherche au sein de la National Autistic Society, a par ailleurs déclare ceci au Huffington Post : "Les personnes atteintes d’autisme présentent souvent des problèmes gastro-intestinaux, mais il existe peu de preuves qui suggèrent un lien de causalité entre ces deux conditions. Bien que cette étude identifie des différences entre la flore intestinale des enfants autistes et non autistes, d’autres études portant sur des enfants présentant tout un spectre de symptômes sont nécessaires afin de confirmer l’existence d’un quelconque lien et de comprendre les processus biologiques que cela implique." "Traiter les problèmes gastro-intestinaux peut contribuer à améliorer le comportement de certaines personnes autistes en diminuant l’inconfort physique et le stress. Toutefois, cela doit être considéré comme une méthode complémentaire et non comme un traitement en soi." The Huffington Post , le 10 janvier 2012 http://www.huffingtonpost.co.uk/2012/01/10/bacteria-in-gut-of-autistic-children-different_n_1196455.html
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30 juin 2013 7 30 /06 /juin /2013 07:48
Bonnie Bassler, "Manipulating Quorum Sensing to Control Bacterial Pathogenicity", VWR Distinguished Seminar in Experimental Biology and Joint Seminar with the School of Biology Seminar Series

traduction partielle :

Les bactéries communiquent entre elles par l'intermédiaire de la production et la détection de molécules de signalisation sécrétées appelés auto-inducteurs.

Ce processus de communication de cellule à cellule, appelée «Quorum Sensing», permet aux bactéries de se synchroniser comportement sur une échelle de la population.

Comportements contrôlés par un "quorum sensing" qui sont généralement inefficaces quand entrepris par une bactérie individuelle agissant seule, mais qui deviennent efficaces lorsqu'elles sont menées de concert par le groupe.

Par exemple, le quorum sensing contrôle la virulence, la formation de biofilm, la sporulation et l'échange d'ADN.

Ainsi, le quorum sensing est un mécanisme qui permet aux bactéries de fonctionner comme des organismes multicellulaires.

Les Bactéries Gram-négatives utilisent l'acyl-homosérine lactone (AHL) autoinducers, qui sont détectés par l'un des deux types de récepteurs, les récepteurs LuxR type cytoplasmiques ou des récepteurs LuxN type membranaires.

Nous avons trouvé de petites molécules antagonistes des récepteurs LuxN type qui sont aussi de puissants antagonistes des récepteurs de type LuxR, malgré les différences dans la structure du récepteur, la localisation, la spécificité AHL, et le mécanisme de signalisation.

Des études structurales combinées avec mutagenèse nous ont permis d'identifier les résidus d'acides aminés dans les récepteurs qui sont essentiels pour conférer une activité agoniste et antagoniste de ligands différents.

Notre plus puissant antagoniste quorum-sensing protège les animaux contre la léthalité par quorum-sensing médiée par des bactéries pathogènes validant la notion que le ciblage du quorum sensing a le potentiel pour le développement de médicaments antimicrobiens.


Abstract:
Bacteria communicate with one another via the production and detection of secreted signal molecules called autoinducers. This cell-to-cell communication process, called “Quorum Sensing”, allows bacteria to synchronize behavior on a population-wide scale. Behaviors controlled by quorum sensing are usually ones that are unproductive when undertaken by an individual bacterium acting alone but become effective when undertaken in unison by the group. For example, quorum sensing controls virulence, biofilm formation, sporulation, and the exchange of DNA. Thus, quorum sensing is a mechanism that allows bacteria to function as multi-cellular organisms. Gram-negative bacteria use acyl-homoserine lactone (AHL) autoinducers, which are detected by one of two receptor types, cytoplasmic LuxR-type receptors or membrane-bound LuxN-type receptors. We found small molecule antagonists of LuxN-type receptors that are also potent antagonists of LuxR-type receptors, despite differences in receptor structure, localization, AHL specificity, and signaling mechanism. Structural studies combined with mutagenesis allowed us to pinpoint the amino acid residues in the receptors that are critical for conferring agonist and antagonist activity to different ligands. Our most potent quorum-sensing antagonist protects animals from quorum-sensing-mediated killing by pathogenic bacteria validating the notion that targeting quorum sensing has potential for antimicrobial drug development.
Additional Info:
Dr. Bassler's lab wants to understand quorum sensing: the process of cell-cell communication in bacteria. Quorum sensing involves the production, release, and subsequent detection of chemical signal molecules called autoinducers. This process enables populations of bacteria to regulate gene expression, and therefore behavior, on a community-wide scale. Quorum sensing is wide-spread in the bacterial world, so understanding this process is fundamental to all of microbiology, including industrial and clinical microbiology, and ultimately to understanding the development of higher organisms. Her labs studies of quorum sensing is providing insight into intra- and inter-species communication, population-level cooperation, and the design principles underlying signal transduction and information processing at the cellular level. These investigations are also leading to synthetic strategies for controlling quorum sensing. Our objectives include development of anti-microbial drugs aimed at bacteria that use quorum sensing to control virulence, and improved industrial production of natural products such as antibiotics. They have pursued our goal of understanding bacterial communication by combining genetics, biochemistry, structural biology, chemistry, microarray studies, bioinformatics, modeling, and engineering approaches.




http://cssb.biology.gatech.edu/node/6461
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