Commensal Bacteria-Specific CD4+ T Cell Responses in Health and Disease

Abstract

Over the course of evolution, mammalian body surfaces have adapted their complex immune system to allow a harmless coexistence with the commensal microbiota. The adaptive immune response, in particular CD4+ T cell-mediated, is crucial to maintain intestinal immune homeostasis by discriminating between harmless (e.g., dietary compounds and intestinal microbes) and harmful stimuli (e.g., pathogens). To tolerate food molecules and microbial components, CD4+ T cells establish a finely tuned crosstalk with the environment whereas breakdown of these mechanisms might lead to chronic disease associated with mucosal barriers and beyond. How commensal-specific immune responses are regulated and how these molecular and cellular mechanisms can be manipulated to treat chronic disorders is yet poorly understood. In this review, we discuss current knowledge of the regulation of commensal bacteria-specific CD4+ T cells. We place particular focus on the key role of commensal-specific CD4+ T cells in maintaining tolerance while efficiently eradicating local and systemic infections, with a focus on factors that trigger their aberrant activation.

Circulating and Salivary Antibodies to Fusobacterium nucleatum Are Associated With Cystic Pancreatic Neoplasm Malignancy

“…In spite of this, it is likely that past periodontal insults or dysbiosis are equally important in regulation of immune memory to commensal bacteria. Additional areas to explore include immune memory and tissue resident memory cells ( 42 , 43 ) that should help gain more understanding into the complex dynamics of immune recognition of cancer-associated commensals in individuals at risk of pancreas malignancies.…”

Strategies to Dissect Host-Microbial Immune Interactions That Determine Mucosal Homeostasis vs. Intestinal Inflammation in Gnotobiotic Mice

“…The complex microbiota in normal hosts help stimulate protective homeostatic immune responses that inhibit effector inflammatory response to resident microbial antigens and innate immune agonists (3,9,10). We discuss gnotobiotic techniques that use the strategies outlined in Table 2 to dissect the function of complex microbiota and their components.…”

Transplant associated infections—The role of the gastrointestinal microbiota and potential therapeutic options

“…The intestinal microbiota plays an important role in regulating the immune system . Signals such as T regulatory cell (T regs) and T helper 17 (Th17) cells have been shown to prime immune responses and regulate both pro‐ and anti‐inflammatory host immune responses .…”

“…[17][18][19][20] The intestinal microbiota plays an important role in regulating the immune system. 21,22 Signals such as T regulatory cell (T regs) and T helper 17 (Th17) cells have been shown to prime immune responses and regulate both pro-and anti-inflammatory host immune responses. [21][22][23] It has been shown in mice models that disruption of the gastrointestinal microbiota with antimicrobial therapy results in a higher proportion of Treg cells in the small intestines and a reduction in Th17 cells.…”

“…21,22 Signals such as T regulatory cell (T regs) and T helper 17 (Th17) cells have been shown to prime immune responses and regulate both pro-and anti-inflammatory host immune responses. [21][22][23] It has been shown in mice models that disruption of the gastrointestinal microbiota with antimicrobial therapy results in a higher proportion of Treg cells in the small intestines and a reduction in Th17 cells. 23 At the same time, it was shown that Treg cells were restored by colonizing the germfree mice with a mixture of Clostridial strains, which led to an induction of IL-10, an anti-inflammatory cytokine, and CTLA4, a molecule which inhibits T cell activation.…”