Compartmentalized Control of Skin Immunity by Resident Commensals

Abstract

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.

The pathogenBatrachochytrium dendrobatidisdisturbs the frog skin microbiome during a natural epidemic and experimental infection

“…conditions (13,14,42,51,52), but are rarely documented during natural outbreaks of known infectious pathogens in the wild. A few studies have demonstrated associations between pathogen infection and bacterial diversity (53) or the abundance of certain cultured isolates in the field (39), but it is often challenging to determine whether observational correlations stem from microbiome variation affecting resistance to pathogen infection or, instead, from pathogen infection altering the microbiome.…”

“…In the figures, OTU relative abundance data are shown untransformed to provide an intuitively meaningful display of original data. Analyses of relative abundances of individual OTUs were performed using only common OTUs, defined as OTUs present in at least 25% of samples in the population, survey visit, or experiment being analyzed (yielding 51,50,38,68,33, and 60 common OTUs in the Marmot, Mono, Unicorn, Conness, Experiment, and Temporal analyses, respectively). The effect on type I statistical error of individually testing multiple OTUs (i.e., multiple comparisons) was accounted for by calculating the false discovery rate, Q, using the program Qvalue (76) and applying a maximum threshold of Q = 0.05 (77).…”

New insights in the pathogenesis of atopic dermatitis

“…Bacterial components have been found in deeper skin compartments including the dermis, suggesting that the microbiome of the skin may extend beyond the skin surface (63). A mouse model showed that Staphylococcus epidermidis differentially upregulates the expression of IL-17 in the skin, rather than in the gut (64), suggesting a specific role of this bacteria in skin immunity. It has been shown that S. epidermidis may produce its own antimicrobial peptides that modulate the survival of other cutaneous microbial pathogens (65,66).…”

Investigating a holobiont: Microbiota perturbations and transkingdom networks

“…One protocol using a cocktail of 4 antibiotics for 4-5 weeks has been exceptionally popular among investigators and allowed to demonstrate the involvement of microbiota in host functions and disease pathogenesis in a variety of models. [29][30][31][32] Furthermore, a few studies compared both germfree and antibiotic-treated animals and detected concordant results. 31,33 However, concordant results are not always observed between these 2 models.…”