NK cells contribute to reovirus-induced IFN responses and loss of tolerance to dietary antigen

Abstract

Celiac disease is an immune-mediated intestinal disorder that results from loss of oral tolerance (LOT) to dietary gluten. Reovirus elicits inflammatory Th1 cells and suppresses Treg responses to dietary antigen in a strain-dependent manner. Strain type 1 Lang (T1L) breaks oral tolerance, while strain type 3 Dearing reassortant virus (T3D-RV) does not. We discovered that intestinal infection by T1L in mice leads to the recruitment and activation of NK cells in mesenteric lymph nodes (MLNs) in a type I IFN–dependent manner. Once activated following infection, NK cells produce type II IFN and contribute to IFN-stimulated gene expression in the MLNs, which in turn induces inflammatory DC and T cell responses. Immune depletion of NK cells impairs T1L-induced LOT to newly introduced food antigen. These studies indicate that NK cells modulate the response to dietary antigen in the presence of a viral infection.

Outsourcing preparatory work based on a systematic literature review for the development of adverse outcome pathways (AOPs) relevant for the capacity of proteins to trigger celiac disease

“…These studies provide a detailed insight into the role of viruses, specifically reovirus (Bouziat et al, 2017;Brigleb et al, 2022) and rotavirus (Zanoni et al, 2006), in CD. Both viruses trigger immune responses that disrupt immune homeostasis in the intestine, leading to an aberrant immune response, which contribute to the characteristic intestinal inflammation of www.efsa.europa.eu/publications EFSA Supporting publication 2024:EN-8570…”

Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus

“…PirB also is expressed by myeloid cells, including B cells, dendritic cells, granulocytes, macrophages, mast cells, and monocytes 61 . It is not clear whether reovirus is capable of infecting these cell types, but infectious reovirus is detectable in CD45 + immune cells isolated from mice infected with T1 reovirus 62 . Therefore, it would be informative to investigate whether PirB serves as an entry receptor for T1 reovirus on immune cells and contributes to blockade of immunological tolerance to newly introduced food antigen, which is associated with T1 reovirus infection 63 .…”

“…Recombinant reoviruses, including two glycan-blind strains (T1SA- and T3SA-) and glycan-binding strain (T3SA+) were recovered by plasmid rescue using reverse genetics in previous studies 41 , 89 . Reovirus propagation, plaque assay titration, and ISVP preparation were conducted as described 34 , 41 , 62 . Purification of reovirus virions was conducted as described previously (dx.doi.org/10.17504/protocols.io.vj7e4rn).…”

Viruses and celiac disease: what do we know ?

“…NK cells also have a role in the loss of tolerance. Indeed, depletion of NK cells impairs T1L-induced loss of tolerance to newly introduced food antigen in mice [68].…”