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Type I IFNs facilitate innate immune control of the opportunistic bacteria Burkholderia cenocepacia in the macrophage cytosol
Authors:Michael G. Dorrington  Clinton J. Bradfield  Justin B. Lack  Bin Lin  Jonathan J. Liang  Tregei Starr  Orna Ernst  Julia L. Gross  Jing Sun  Alexandra H. Miller  Olivia Steele-Mortimer  Iain D. C. Fraser
Affiliation:1. Signaling Systems Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, Maryland, United States of America;2. NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, NIH, Frederick, Maryland, United States of America;3. Salmonella-Host Cell Interactions Section, Laboratory of Bacteriology, NIAID, NIH, Hamilton, Montana, United States of America;Children’s Hospital Boston, UNITED STATES
Abstract:The mammalian immune system is constantly challenged by signals from both pathogenic and non-pathogenic microbes. Many of these non-pathogenic microbes have pathogenic potential if the immune system is compromised. The importance of type I interferons (IFNs) in orchestrating innate immune responses to pathogenic microbes has become clear in recent years. However, the control of opportunistic pathogens–and especially intracellular bacteria–by type I IFNs remains less appreciated. In this study, we use the opportunistic, Gram-negative bacterial pathogen Burkholderia cenocepacia (Bc) to show that type I IFNs are capable of limiting bacterial replication in macrophages, preventing illness in immunocompetent mice. Sustained type I IFN signaling through cytosolic receptors allows for increased expression of autophagy and linear ubiquitination mediators, which slows bacterial replication. Transcriptomic analyses and in vivo studies also show that LPS stimulation does not replicate the conditions of intracellular Gram-negative bacterial infection as it pertains to type I IFN stimulation or signaling. This study highlights the importance of type I IFNs in protection against opportunistic pathogens through innate immunity, without the need for damaging inflammatory responses.
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