In the absence of commensal microbiota, mice have been shown to be unable to efficiently resist infections at different anatomical sites, such as influenza A in the lung and oral Listeria infection [21, 25, 26, 53, 58]. Mice lacking commensal microbiota have also been shown not to develop pathology in experimental models of autoimmunity, such as those for multiple PD-1 inhibiton sclerosis and arthritis [59-61]. These mice have also been shown to respond poorly to different types of cancer immune- and chemotherapy [22, 62]. Although the precise mechanisms behind these observations still need to be clarified, GF or antibiotics-treated animals have been shown to have a reduced number of different subsets of T cells,

such as Th1 and Th17 cells constitutively producing IFN-γ and IL-17, respectively. They also present an expansion of Treg cells, and fail to activate innate resistance and adaptive immunity responses to systemic infections [20, 21, 53, 26]. Thus, in the absence of the commensal microbiota, a decreased Selleckchem Tyrosine Kinase Inhibitor Library inflammatory and immune setting is established, which is lower than that required for optimal responses to stimuli. While the microbiota at all barrier surfaces is likely able to contribute

to local immunity [57], the systemic immune homeostatic effect of the microbiota has been largely ascribed to the gut microbiota [21, 25]. Colonization of the skin of GF mice with bacterial species that efficiently reconstitute skin immunity has been shown to have no systemic effect, for example, skin bacterial

colonization does not enhance the activation of Th1 cells and Th17 cells in the intestinal lamina propria [53]. The possible predominant effect of the gut microbiota at the systemic level may be due to its higher diversity and higher total number of microorganisms (up to a trillion) than that in other organ [63], as well as to the large surface area that the gut mucosa and the associated Celecoxib immune organs comprise. However, because most experimental evidence is based on the use of GF mice or use of oral antibiotics that may deplete the microbiota at sites other than the gut, for example, in the oral cavity, it is possible that the microbiota at all barrier sites in combination may contribute to the observed systemic effects. Moreover, despite the great variation among microbiota at different body sites, the community types present at the different anatomical barriers have been found to be predictive of each other [64]: thus, it is possible that the observation of a correlation between a particular immune phenotype and the microbiota of a given organ, for example, the gut, may reflect the contribution of other organs, for example, the oral cavity. The epithelial barrier is maintained not only by the presence of tight junctions among epithelial cells and physicochemical barriers, such as keratin and mucous layers, but also by active mechanisms mediated by soluble products (e.g.