Microbial Ecology in States of Health and Disease Workshop Summary (2014) / Chapter Skim
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A1 Effector and memory T cell responses to commensal bacteria--Yasmine Belkaid, Nicolas Bouladoux, and Timothy W. Hand
A1 Effector and memory T cell responses to commensal bacteria--Yasmine Belkaid, Nicolas Bouladoux, and Timothy W. Hand
Pages 93-109
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From page 93... ...
Regulation of immune responses to this enormous antigenic load represents a tremendous challenge for the immune system. Tissues exposed to commensals have developed elaborate systems of regulation including specialized populations of resident lymphocytes that maintain barrier function and limit potential responses to commensal antigens.
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From page 94... ...
and control many aspects of host physiology, not the least of which are lymphocytes of the immune system. T cells are found in large numbers lining barrier surfaces where they are tasked with surveillance against infection while maintaining diplomatic relations with the resident commensal microbiota (Hooper et al., 2012)
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From page 95... ...
The microbiota encodes millions of proteins, each of them expressing several potential foreign antigens directly associated with inflammatory pathogen-associated molecular patterns. This enormous antigenic load represents a tremendous challenge for barrier immunity as unwanted responses against these antigens could lead to severe pathological consequences.
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From page 96... ...
. IgA can directly modulate expression of commensal antigens and mucosal association, therefore, this implies that Treg cells may play multiple and complementary roles in controlling the host relation with the microbiota (Peterson et al., 2007; Suzuki et al., 2004)
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From page 97... ...
cells. Commensal-specific Treg cells traffic to the lamina propria and Peyer's patches, where they, along with polyclonal Treg cells, can regulate effector T cell responses and induce class switching and IgA production from resident commensal-specific B cells, reinforcing the commensal barrier.
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From page 98... ...
Although these data support the notion that the flora promotes the induction and/ or maintenance of T cells in the GI tract independent of antigen specificity, they do not exclude that a significant portion of mucosal T cells recognize commensal antigens and the specificity of Th1, Th17, or Treg cells that reside at barrier sites under physiological settings remains an important open question. Environmentally Induced Shifts in the Microbiota Active regulation of immune tolerance to the commensal microbiota is a lifelong process, because, in contrast to the host genome, the commensal microbiota is not fixed.
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From page 99... ...
. In mouse models, this system has been proven extraordinarily robust because only complete deficiency of key innate and adaptive mucosal immune mechanisms leads to systemic commensal specific antibody responses (Slack et al., 2009)
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From page 100... ...
Commensal-Specific Memory T Cell Responses One remarkable feature of all barrier sites is their ability to repair efficiently after inflammation or breach. In the GI tract, this implies that after acute tissue damage and transiently increased exposure to commensals, physical segregation between the flora and the immune system is rapidly restored.
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From page 101... ...
. Exploration of the antigen specificity of the memory cell compartment of lymphocytes residing at all barrier sites would inform us of the potential impact of these commensal-specific T cell responses on tissue physiology and subsequent pathologies.
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From page 102... ...
, immune responses against the invading agent can be associated with specific T cell responses against a large number of coincident commensal antigens. These commensal-specific effector T cell responses can persist as memory cells that upon subsequent infection will be recalled as secondary commensal-specific effectors, alongside the priming of a novel immune response to the invasive pathogen.
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From page 103... ...
. One key point taken from these studies is that multiple bacterial types comprising several distantly related bacterial phyla can promote colitis, possibly via the induction of specific CD4 T cell responses, supporting the idea that IBD may develop as a consequence of a broad loss of tolerance to the commensal microbiota (Sartor, 2006)
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From page 104... ...
One might speculate that the coevolution between the adaptive immune system and commensal microbiota was primarily driven by the difficulty of maintaining and controlling such a complex relationship. However, barrier surfaces are not static and are often perturbed by environmental or infectious challenges, causing changes to the commensal microbiota and increasing tissue permeability.
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(2011) Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease.
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(2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses.
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(2004) Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria.
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(2011) Intestinal homeostasis and its breakdown in inflammatory bowel disease.
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From page 109... ...
(2012) Innate lymphoid cells promote anatomical containment of lymphoid resident commensal bacteria.
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