An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System
The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.
Compartmentalized Control of Skin Immunity by Resident Commensals
Skin Specifics Much of the recent attention paid to the trillions of bacteria that colonize our bodies has been given to the bacteria that reside in the gut. Naik et al. (p. 1115, published online 26 July) report that colonization of the skin with commensal bacteria is important for tuning effector T cell responses in the skin and for protective immunity against cutaneous infection with the parasite Leishmania major in mice. In contrast, selective depletion of the gut microbiota, which plays an important role in modulating immune responses in the gut, had no impact on T cell responses in the skin. The skin microbiota play a selective role in modulating immunity in the skin of mice. Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.
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