Work

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

Year: 2019

Type: article

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 targets for colonic infections, inflammatory bowel disease, and promotion of mucosal vaccine efficacy. Author summaryDiarrheal diseases still remain the second leading cause of mortality in children younger than 5 years old worldwide, leading to 1.3 million deaths per annum.The diarrheagenic Escherichia coli (DEC) pathotypes are considered NIAID Biodefense Category B agents.Human infections with enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) are associated with human disease.EPEC is a common cause of infantile diarrhea in the developing and underdeveloped world, and EHEC is considered an emerging zoonotic infection.These enteric pathogens cause a wide range of clinical symptoms, varying from mild diarrhea to more complicated clinical presentations, including hemolytic-uremic syndrome (HUS) and hemorrhagic colitis.Using a murine

Source: PLoS Pathogens

DOI: 10.1371/journal.ppat.1007614

Authors: Shahram Solaymani-Mohammadi, Jay A. Berzofsky

Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research

Language: English

Topic: interferon and immune responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,350