The mammalian gastrointestinal tract can harbor both beneficial commensal bacteria important for host health, but also pathogenic bacteria capable of intestinal damage. It is therefore important that the host immune system mount the appropriate immune response to these divergent groups of bacteria–promoting tolerance in response to commensal bacteria and sterilizing immunity in response to pathogenic bacteria. Failure to induce tolerance to commensal bacteria may underlie immune-mediated diseases such as human inflammatory bowel disease. At homeostasis, regulatory T (Treg) cells are a key component of the tolerogenic response by adaptive immunity. This review examines the mechanisms by which intestinal bacteria influence colonic T cells and B cell IgA induction, with an emphasis on Treg cells and the role of antigen-specificity in these processes. In addition to discussing key primary literature, this review highlights current controversies and important future directions.

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cells responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. Here, we addressed this by analyzing bacterial-reactive TCR transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg responses during homeostasis and Teff responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis. In fact, 4/6 Treg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion of luminal Bacteroides species seen during colitis did not trigger a commensurate Teff response. Unlike other Treg cell-inducing bacteria, Helicobacter species are known pathobionts and cause disease in immunodeficient mice. Thus, our study suggests a model in which mucosal bacteria elicit context-dependent Treg or effector cell responses to facilitate intestinal tolerance or inflammation.

Aberrant immune responses against gut microbiota are thought to be key drivers of inflammatory bowel disease (IBD) pathogenesis. However, the extent and targets of immunoglobulin (Ig) A versus IgG responses to gut bacteria in IBD and its association with IBD severity is not well understood. Here, we address this by analyzing fecal samples from Crohn's disease (CD), ulcerative colitis (UC), and Non-IBD patients by flow cytometry for the frequency of bacteria that were endogenously bound with IgA and/or IgG. Assessment of IBD patients from two geographically distinct cohorts revealed increased percentages of IgA-and IgG-bound fecal bacteria compared to non-IBD controls. Notably, the two major subsets of IBD showed distinct patterns of Ig-bound bacteria, with CD activity associated with increases in both IgA and IgG-bound bacteria, whereas UC activity correlated only with increases in IgG-bound bacteria. Analysis of the flow sorted Igbound bacterial repertoire by 16S rDNA sequencing revealed taxa that were Ig-bound specifically in IBD. Notably, this included bacteria that are also thought to reside in the oral pharynx, including Gemella, Peptostreptococcus, and Streptococcus species. These data show that the pattern of IgA and IgG binding to fecal bacteria is distinct in UC and CD. In addition, the frequency of Ig-bound fecal bacteria may have potential as a non-invasive biomarker for disease activity. Finally, our results support the hypothesis that immune responses to oral pharyngeal bacteria may play an important role in the pathogenesis of IBD.

Cerebral sparganosis is a rare cestode larval parasitic infestation of the nervous system. We report a 28-year-old female from South India with a temporo-occipital mass lesion, which mimicked a tuberculoma on imaging. She received antituberculous therapy for 7 months. Surgical excision of the mass revealed a parasitic abscess containing larval form of Sparganum mansoni. Cerebral sparganosis can closely mimic tuberculoma or neoplastic lesions. Hence, in areas endemic for tuberculosis, such as India, it is appropriate to suggest that histological diagnosis be sought in tuberculoma mimicking lesions, especially when the lesion is not responding to treatment.

Highlights d Stress in mice causes diarrhea, dysbiosis, barrier defect, increased antibacterial IgA d Stress-induced microbial changes are sufficient to elicit the above effects d IBS-D patients from two cohorts display increased and unique antibacterial IgA d Antibacterial IgA in IBS-D correlates with patient symptom severity