Editors' ChoiceMicrobiome

Immunological Transference: Commensals Get Kicked

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Science Translational Medicine  03 Oct 2012:
Vol. 4, Issue 154, pp. 154ec176
DOI: 10.1126/scitranslmed.3005011

The classic device to explain psychological transference involves a bad day at work that results in a dog being kicked. New work by Hand et al. indicates that the mammalian immune system may also engage in a type of transference. The authors show that gastrointestinal pathogens can incite an immune response that is directed against both the pathogens and the commensal gastrointestinal bacteria required for appropriate bowel function.

The immune system must allow commensal organisms to survive in the bowel while keeping them from entering other body spaces. How gastrointestinal infection upsets this balance is not well understood. Hand et al. examined this question by infecting mice with a parasite and tracking the expansion of T cells that recognized commensal organisms but not the parasite. These commensal-specific T cells expanded upon parasitic infection, indicating that the adaptive immune system is unable to discriminate pathogens from commensal microbes during infection. Despite clearance of the parasite from the bowel, as determined by fluorescence microscopy, activated commensal-specific T cells persisted.

The observation that T cells that mediated the immune attack of commensal organisms lasted long after the pathogen had left the bowel provides a new bit of evidence that supports a clinical association between infection and autoimmunity. However, wild-type mice did not show evidence of inflammatory bowel pathology after the parasitic infection was cleared, despite the presence of these T cells. It is possible that the commensal-specific T cells could cause mucosal pathology by attacking mucosal commensal bacteria. Whether chronic exposure of commensal-specific T cells to their target bacteria inactivates these T cells or whether active immuoregulatory mechanisms restrain commensal-specific immunity are future research questions that will provide a mechanism for prevention of immunopathology from “immune transference.”

T. W. Hand et al., Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 337, 1553–1556 (2012). [Full Text]

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