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 8

NK cells contribute to T1L-induced T cell priming responses associated with LOT to dietary antigen early following inoculation.

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NK cells contribute to T1L-induced T cell priming responses associated w...
WT mice i.p. injected with either isotype control IgG2a Ab or anti-NK1.1 Ab (PK136) 1 day prior to and 1 day following PO inoculation with 1 × 108 PFU of T1L or PBS as a control. OT-II T cells were transferred from CD45.1+ WT mice to CD45.2+ WT mice 1 day prior to reovirus inoculation. At 3 dpi, MLNs were resected and processed for flow cytometry (n = 5–6). (A) Contour plot of OT-II T cell expression of transcription factors Tbet (y-axis), indicating a Th1 phenotype, and Foxp3 (x-axis), indicating a Treg phenotype. (B) Total number and frequency of Treg (Tbet–, Foxp3+) OT-II CD4+ T cells (CD45.1+ CD4+). (C) Total number and frequency of Th1 (Tbet+, Foxp3–) OT-II CD4+ T cells (CD45.1+ CD4+). 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 B and C. *P < 0.05; ****P < 0.0001.