Interleukin 21 collaborates with interferon-γ for the optimal expression of interferon-stimulated genes and enhances protection against enteric microbial infection

PLoS Pathogens
Shahram Solaymani-Mohammadi, Jay A Berzofsky

Abstract

The mucosal surface of the intestinal tract represents a major entry route for many microbes. Despite recent progress in the understanding of the IL-21/IL-21R signaling axis in the generation of germinal center B cells, the roles played by this signaling pathway in the context of enteric microbial infections is not well-understood. Here, we demonstrate that Il21r-/- mice are more susceptible to colonic microbial infection, and in the process discovered that the IL-21/IL-21R signaling axis surprisingly collaborates with the IFN-γ/IFN-γR signaling pathway to enhance the expression of interferon-stimulated genes (ISGs) required for protection, via amplifying activation of STAT1 in mucosal CD4+ T cells in a murine model of Citrobacter rodentium colitis. As expected, conditional deletion of STAT3 in CD4+ T cells indicated that STAT3 also contributed importantly to host defense against C. rodentium infection in the colon. However, the collaboration between IL-21 and IFN-γ to enhance the phosphorylation of STAT1 and upregulate ISGs was independent of STAT3. Unveiling this previously unreported crosstalk between these two cytokine networks and their downstream genes induced will provide insight into the development of novel therapeutic...Continue Reading

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Citations

Sep 22, 2019·Nature Reviews. Microbiology·Caroline Mullineaux-SandersGad Frankel
Dec 24, 2019·Frontiers in Cellular and Infection Microbiology·Shahram Solaymani-MohammadiSteven M Singer
Mar 5, 2021·International Journal of Medical Microbiology : IJMM·Iris StolzerClaudia Günther

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Methods Mentioned

BETA
targeted mutation
ELISA
IECs
flow cytometry
Flow
FACS
PMA

Software Mentioned

GraphPad Prism
Morpheus
Nanostring
GraphPad
Aperio ImageScope
FlowJo
nSolver

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