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Infect Immun. 2017 Oct 18;85(11). pii: e00570-17. doi: 10.1128/IAI.00570-17. Print 2017 Nov.

Induction of Type I Interferon through a Noncanonical Toll-Like Receptor 7 Pathway during Yersinia pestis Infection.

Author information

1
Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA.
2
Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA andersondeb@missouri.edu.

Abstract

Yersinia pestis causes bubonic, pneumonic, and septicemic plague, diseases that are rapidly lethal to most mammals, including humans. Plague develops as a consequence of bacterial neutralization of the host's innate immune response, which permits uncontrolled growth and causes the systemic hyperactivation of the inflammatory response. We previously found that host type I interferon (IFN) signaling is induced during Y. pestis infection and contributes to neutrophil depletion and disease. In this work, we show that type I IFN expression is derived from the recognition of intracellular Y. pestis by host Toll-like receptor 7 (TLR7). Type I IFN expression proceeded independent of myeloid differentiation factor 88 (MyD88), which is the only known signaling adaptor for TLR7, suggesting that a noncanonical mechanism occurs in Y. pestis-infected macrophages. In the murine plague model, TLR7 was a significant contributor to the expression of serum IFN-β, whereas MyD88 was not. Furthermore, like the type I IFN response, TLR7 contributed to the lethality of septicemic plague and was associated with the suppression of neutrophilic inflammation. In contrast, TLR7 was important for defense against disease in the lungs. Together, these data demonstrate that an atypical TLR7 signaling pathway contributes to type I IFN expression during Y. pestis infection and suggest that the TLR7-driven type I IFN response plays an important role in determining the outcome of plague.

KEYWORDS:

IFN-β; MyD88; TLR7; Yersinia pestis; YopJ; plague; type I interferon

PMID:
28847850
PMCID:
PMC5649010
DOI:
10.1128/IAI.00570-17
[Indexed for MEDLINE]
Free PMC Article

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