Editors' ChoiceIMMUNITY

Microbiota and Immune Cells: Friends with Benefits

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Science Translational Medicine  04 Jul 2012:
Vol. 4, Issue 141, pp. 141ec119
DOI: 10.1126/scitranslmed.3004532

The hygiene hypothesis reasons that humans who grow up in increasingly developed and sterilized environments may acquire abnormal immune responses that result in autoimmune and allergic diseases. Now, Chung et al. substantially alter this paradigm by demonstrating that the mammalian immune system befriends specific microbes in the normal microbiota, a relationship that directly benefits the host by providing proper immune education and maturation.

Chung et al. investigated the gut immune systems of germ-free mice and compared them with animals with normal mouse microbiota and mice transplanted with normal human microbiota. Germ-free mice had limited T lymphocytes in intestinal tissue and secondary gut lymphoid tissues such as Peyer's patches. Similarly, mice transplanted with human or rat microbiota also lacked intestinal and Peyer's patch T cells. Distant secondary lymphoid tissues, such as spleen and skin-draining lymph nodes, were not affected by changes in gut flora. Naïve lymphocytes predominated in mice with human microbiota; however, normal mouse microbiota stimulated proliferation of effector/memory CD4+ T cells within secondary gut lymphoid tissues. These effector lymphocytes expressed gut-specific homing markers, suggesting that T cells are activated in the gut secondary lymph tissue and imprinted to traffic to the intestine. Distinct lymphocyte phenotypes resulted from different microbiota, with human flora enhancing a TH2 or allergy-prone response, whereas normal mouse microbiota shifted T cells toward the TH17 pathway. Last, the authors demonstrated that germ-free and human microbiota–containing mice were unable to contain Salmonella, a common enteral pathogen, which did not cause disease in normal mice. Together, these results demonstrate a mutually beneficial relationship that requires species-specific microbes to educate the normal host immune system.

The ability of germs, or lack of germs, to alter immune function has long been recognized; however, we now know that specific microbe-host interactions are more important than merely the quantity of microbes or antigen exposures. The new data suggest that specific microbes could be used to reeducate the gut immune system to either treat disease or, better yet, prevent its occurrence.

H. Chung et al., Gut immune maturation depends on colonization with a host-specific microbiota. Cell 149, 1578–1593 (2012). [Abstract]

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