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We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 1012/g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function. [ABSTRACT FROM AUTHOR]

The distribution and dynamic changes of CD4+ CD25+ Fox P3+ and CD4+ CD25− Fox P3+ regulatory T (Treg) cells induced by human rotavirus ( HRV) infection and vaccination were examined in neonatal gnotobiotic pigs infected with virulent HRV (Vir HRV) or vaccinated with attenuated HRV (Att HRV). Subsets of gnotobiotic pigs in the Att HRV and control groups were challenged with Vir HRV at post-inoculation day ( PID) 28. We demonstrated that Vir HRV infection or Att HRV vaccination reduced frequencies and numbers of tissue-residing Treg cells, and decreased the frequencies of interleukin-10 ( IL-10) and transforming growth factor-β ( TGF-β) producing CD4+ CD25− Treg cells in ileum, spleen and blood at PID 28. The frequencies of IL-10 and TGF-β producing CD4+ CD25− Treg cells in all sites at PID 28 were significantly inversely correlated with the protection rate against Vir HRV-caused diarrhoea ( r = −1, P < 0·0001). Hence, higher frequencies of functional CD4+ CD25− Treg cells can be an indicator for poorer protective immunity against rotavirus. Our results highlighted the importance of CD4+ CD25− Treg cells over CD4+ CD25+ Treg cells in rotavirus infection and immunity. Att HRV vaccination (induction of immune effector responses) reduced the expansion of CD4+ CD25− Treg cells in ileum seen in the challenged naive pigs during the acute phase of Vir HRV infection and preserved normal levels of intestinal TGF-β producing Treg cells post-challenge. The reduced suppressive effect of Treg cells in Att HRV-vaccinated pigs would unleash effector/memory T-cell activation upon challenge. Preserving TGF-β producing CD4+ CD25− Treg cells is important in maintaining homeostasis. Based on our findings, a model is proposed to depict the dynamic equilibrium course of Treg and effector T-cell responses after primary rotavirus infection/vaccination and challenge. [ABSTRACT FROM AUTHOR]

To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10 (IL-10) mice. No typhlocolitis developed in germ-free controls ( n = 21) or in L. reuteri ( n = 8) or H. hepaticus ( n = 18) mono-associated mice for 20 weeks post-infection. As positive controls, three specific pathogen-free IL-10 mice dosed with H. hepaticus developed severe typhlocolitis within 11 weeks. Because L. reuteri PTA-6475 has anti-inflammatory properties in vitro, it was unexpected to observe significant typhlocolitis ( P < 0·0001) in mice that had been infected with L. reuteri followed in 1 week by H. hepaticus ( n = 16). The H. hepaticus colonization was not affected through 20 weeks post-infection but L. reuteri colonization was lower in co-infected compared with L. reuteri mono-associated mice at 8-11 weeks post-infection ( P < 0·05). Typhlocolitis was associated with an increased T helper type 1 serum IgG2c response to H. hepaticus in co-infected mice compared with H. hepaticus mono-associated mice ( P < 0·005) and similarly, mRNA expression in caecal-colonic tissue was elevated at least twofold for chemokine ligands and pro-inflammatory interleukin-1α (IL-1α), IL-1β, IL-12 receptor, tumour necrosis factor-α and inducible nitric oxide synthase. Anti-inflammatory transforming growth factor-β, lactotransferrin, peptidoglycan recognition proteins, Toll-like receptors 4, 6, 8 and particularly 9 gene expression, were also elevated only in co-infected mice ( P < 0·05). These data support that the development of typhlocolitis in H. hepaticus-infected IL-10 mice required co-colonization with other microbiota and in this study, required only L. reuteri. Although the effects other microbiota may have on H. hepaticus virulence properties remain speculative, further investigations using this gnotobiotic model are now possible. [ABSTRACT FROM AUTHOR]