Opposing Roles for Interferon Regulatory Factor-3 (IRF-3) and Type I Interferon Signaling during Plague

PLoS Pathogens

Ami A. Patel¹  Deborah M. Anderson¹  Jennifer Hughes-Hanks¹  Hanni Lee-Lewis²  Craig A. Lewis² 

[1] Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America;Laboratory for Infectious Disease Research, University of Missouri, Columbia, Missouri, United States of America

关键词: Yersinia pestis;    Neutrophils;    Cytokines;    Macrophages;    Spleen;    Interferons;    Phagocytosis;    Bacterial pathogens;   

DOI  :  10.1371/journal.ppat.1002817

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Type I interferons (IFN-I) broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs) following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-β was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-β following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-β signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-β production.

【 授权许可】

CC BY