3 years ago

Induction of type I interferon through a non-canonical Toll-like receptor 7 pathway during Yersinia pestis infection.

Anderson DM, Dhariwala MO, Olson RM
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 to TLR7, suggesting a non-canonical mechanism occurs in Y. pestis infected macrophages. In the murine plague model, TLR7 was a significant contributor to the expression of serum IFNβ whereas MyD88 was not. Furthermore, like the type I IFN response, TLR7 contributed to lethality of septicemic plague and was associated with the suppression of neutrophilic inflammation. In contrast, TLR7 was important to defense against disease in the lungs. Together the 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.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28847850

DOI: PubMed:28847850

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