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 1

Reovirus strains differ in NK cell infiltration and general activation in GALT early following inoculation.

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Reovirus strains differ in NK cell infiltration and general activation i...
WT mice were PO inoculated with 1 × 108 PFU of T1L or T3D-RV or PBS as a control. At 2 dpi, MLNs and PPs were resected and processed for flow cytometry and determination of viral titer in a 3 cm section of ileal tissue to ensure titer-matched samples. Single-cell suspensions were stained with a comprehensive Ab panel and analyzed by flow cytometry (n = 6–11). (A) Total immune cells (CD 45+) in MLNs or PPs following inoculation. (B) Dot plots of representative samples of NK cells (CD45+ TCRβ– NK1.1+) in MLNs at 2 dpi. (C) Total cell count and percent of NK cells (CD45+ TCRβ– NK1.1+) in MLNs and PPs. (D) Total number and percent of activated CD69-expressing NK cells in MLNs. (E) Total number and percent of activated CD69-expressing NK cells in PPs. 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 and C–E. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.