NK cells contribute to reovirus-induced IFN responses and loss of tolerance to dietary antigen
Pamela H. Brigleb, Elaine Kouame, Kay L. Fiske, Gwen M. Taylor, Kelly Urbanek, Luzmariel Medina Sanchez, Reinhard Hinterleitner, Bana Jabri, Terence S. Dermody
Pamela H. Brigleb, Elaine Kouame, Kay L. Fiske, Gwen M. Taylor, Kelly Urbanek, Luzmariel Medina Sanchez, Reinhard Hinterleitner, Bana Jabri, Terence S. Dermody
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Research Article Immunology Virology

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.

Authors

Pamela H. Brigleb, Elaine Kouame, Kay L. Fiske, Gwen M. Taylor, Kelly Urbanek, Luzmariel Medina Sanchez, Reinhard Hinterleitner, Bana Jabri, Terence S. Dermody

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Figure 3

NK cells are not susceptible to reovirus infection and are recruited from the bone marrow and do not increase proliferation at site of infection.

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NK cells are not susceptible to reovirus infection and are recruited fro...
(A) WT mice were PO inoculated with 1 × 108 PFU of T1L or T3D-RV or PBS as a control. At 2 dpi, single-cell suspensions from MLNs were sorted by flow cytometry to obtain live, CD45+ immune cells or NK1.1+Tcrβ– NK cells and processed for viral titer by plaque assay (n = 6). (B) WT mice were PO inoculated with 1 × 108 PFU of T1L or PBS as a control. At 2 dpi, the spleen was resected and processed for flow cytometry to determine the number of NK cells in the spleen (n = 7). (C) WT mice were PO inoculated with 1 × 108 PFU of T1L or PBS as a control. At 2 dpi, MLNs were resected and processed for flow cytometry and were assessed for ki67 marker of proliferation by intracellular cytokine staining (n = 6). (D) Representative contour plots of ki67 staining in NK cells (CD45+ Tcrβ– NK1.1+ DX5+ ki67+). Results are presented as mean values. Data are shown as mean ± SEM. Statistical significance was calculated using 1-way ANOVA with Tukey’s multiple comparisons test in A or using Student’s t test in B and C. **P < 0.01; ****P < 0.0001.