Compartmentalized Control of Skin Immunity by Resident Commensals

Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Science (Impact Factor: 33.61). 07/2012; 337(6098):1115-9. DOI: 10.1126/science.1225152
Source: PubMed


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.

Download full-text


Available from: Nicolas Bouladoux,
1 Follower
119 Reads
  • Source
    • "Studies have indicated that treatment with the antibiotic vancomycin decreases Th17 populations in the small intestine of conventional mice (103, 112), whereas treatment with a complex cocktail of antibiotics, results in a decreased Th17 frequency in the mesenteric lymph node (113). In other mucosal sites, such as the skin, resident commensal microbiota have been shown to induce Th17 and Th1 differentiation to protect the host from pathogens and possible opportunistic microbes (114). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vertebrates have co-evolved with microorganisms resulting in a symbiotic relationship, which plays an important role in health and disease. Skin and mucosal surfaces are colonized with a diverse population of commensal microbiota, over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years, studies have built on the idea that commensal microbiota is in constant contact with the host immune system and thus influence immune function. Recent studies, focusing on mutualism in the gut, have shown that commensal microbiota seems to play a critical role in the development and homeostasis of the host immune system. In particular, the gut microbiota appears to direct the organization and maturation of lymphoid tissues and acts both locally and systemically to regulate the recruitment, differentiation, and function of innate and adaptive immune cells. While the pace of research in the area of the mucosal-immune interface has certainly intensified over the last 10 years, we are still in the early days of this field. Illuminating the mechanisms of how gut microbes shape host immunity will enhance our understanding of the causes of immune-mediated pathologies and improve the design of next-generation vaccines. This review discusses the recent advances in this field, focusing on the close relationship between the adaptive immune system and commensal microbiota, a constant and abundant source of foreign antigens.
    Frontiers in Immunology 07/2014; 5:318. DOI:10.3389/fimmu.2014.00318
  • Source
    • "In contrast, B cells are rare in healthy skin. Tregs are also found in substantial numbers in healthy mouse dermis and their contribution to immunity or inflammation appears regulated by skin commensals (16). Skin Tregs display a much slower migrational velocity compared with effector CD4+ T cells although acute inflammation results in a rapid increase in their motility (17). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The skin is a large and complex organ that acts as a critical barrier protecting the body from pathogens in the environment. Numerous heterogeneous populations of immune cells are found within skin, including some that remain resident and others that can enter and exit the skin as part of their migration program. Pathogen-specific CD8(+) T cells that persist in the epidermis following infection are a unique population of memory cells with important roles in immune surveillance and protective responses to reinfection. How these tissue-resident memory T cells form in the skin, the signals controlling their persistence and behavior, and the mechanisms by which they mediate local recall responses are just beginning to be elucidated. Here, we discuss recent progress in understanding the roles of these skin-resident T cells and also highlight some of the key unanswered questions that need addressing.
    Frontiers in Immunology 07/2014; 5:332. DOI:10.3389/fimmu.2014.00332
  • Source
    • "This may relate to the fact that skin appendages such as hair follicles, sweat glands, and sebaceous glands house diverse and unique microbial communities that interact with and shape the cutaneous immune system (56). Indeed, there was a pronounced increase in the frequency and number of Treg cells in the skin of germ-free mice, indicating that interactions with cutaneous commensal flora help regulate Treg cell abundance in the skin (57). Moreover, this study demonstrated that commensal-dependent production of IL-1 in the skin is essential for inflammatory immune responses to the parasite Leishmania major, and this may in part be due to the ability of IL-1 to suppress Treg cell function (58). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Foxp3(+) regulatory T cells (Treg cells) are essential for establishing and maintaining self-tolerance, and also inhibit immune responses to innocuous environmental antigens. Imbalances and dysfunction in Treg cells lead to a variety of immune-mediated diseases, as deficits in Treg cell function contribute to the development autoimmune disease and pathological tissue damage, whereas overabundance of Treg cells can promote chronic infection and tumorigenesis. Recent studies have highlighted the fact that Treg cells themselves are a diverse collection of phenotypically and functionally specialized populations, with distinct developmental origins, antigen-specificities, tissue-tropisms, and homeostatic requirements. The signals directing the differentiation of these populations, their specificities and the mechanisms by which they combine to promote organ-specific and systemic tolerance, and how they embody the emerging property of regulatory memory are the focus of this review.
    Frontiers in Immunology 07/2014; 5:333. DOI:10.3389/fimmu.2014.00333
Show more

Similar Publications