Search

Summary: The field of mucosal immunology has, for the last 10 years, been largely dominated by advances in our understanding of the commensal microbiota. Developments of novel experimental methodologies and analysis techniques have provided unparalleled insight into the profound impact the microbiota has on the development and function of the immune system. In this cross‐journal review series published in Immunology and Clinical and Experimental Immunology, we aim to summarize the current state of research concerning the interplay between the microbiota and mucosal immunity. In addition, the series examines how the increased understanding of the microbiota is changing the nature of immunological research, both in the laboratory and in the clinic. [ABSTRACT FROM AUTHOR]

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn’s disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients. [ABSTRACT FROM AUTHOR]

CD4+ T cells have long been grouped into distinct helper subsets on the basis of their cytokine-secretion profile. In recent years, several subsets of innate lymphoid cell have been described as key producers of these same Th-associated cytokines. However, the functional relationship between Th cells and innate lymphoid cells (ILCs) remains unclear. We show in this study that lineagenegative ST2+ICOS+CD45+ type 2 ILCs and CD4+ T cells can potently stimulate each other's function via distinct mechanisms. CD4+ T cell provision of IL-2 stimulates type 2 cytokine production by type 2 ILCs. By contrast, type 2 ILCs modulate naive T cell activation in a cell contact-dependent manner, favoring Th2 while suppressing Th1 differentiation. Furthermore, a proportion of type 2 ILCs express MHC class II and can present peptide Ag in vitro. Importantly, cotransfer experiments show that type 2 ILCs also can boost CD4+ T cell responses to Ag in vivo. [ABSTRACT FROM AUTHOR]

Presentation of peptide:MHCII by RORγ-expressing group 3 innate lymphoid cells (ILC3s), which are enriched within gut tissue, is required for control of CD4 T-cell responses to commensal bacteria. It is not known whether ILC populations migrate from their mucosal and peripheral sites to local draining secondary lymphoid tissues. Here we demonstrate that ILC3s reside within the interfollicular areas of mucosal draining lymph nodes, forming a distinct microenvironment not observed in peripheral lymph nodes. By photoconverting intestinal cells in Kaede mice we reveal constitutive trafficking of ILCs from the intestine to the draining mesenteric lymph nodes, which specifically for the LTi-like ILC3s was CCR7-dependent. Thus, ILC populations traffic to draining lymph nodes using different mechanisms.

Dendritic cells (DCs) play a critical key role in the initiation of immune responses to pathogens. Paradoxically, they also prevent potentially damaging immune responses being directed against the multitude of harmless antigens, to which the body is exposed daily. These roles are particularly important in the intestine, where only a single layer of epithelial cells provides a barrier against billions of commensal microorganisms, pathogens, and food antigens, over a huge surface area. In the intestine, therefore, DCs are required to perform their dual roles very efficiently to protect the body from the dual threats of invading pathogens and unwanted inflammatory reactions. In this review, we first describe the biology of DCs and their interactions with other cells types, paying particular attention to intestinal DCs. We, then, examine the ways in which this biology may become misdirected, resulting in inflammatory bowel disease. Finally, we discuss how DCs potentiate immune responses against viral, bacterial, parasitic infections, and their importance in the pathogenesis of prion diseases. We, therefore, provide an overview of the complex cellular interactions that affect intestinal DCs and control the balance between immunity and tolerance.