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FPR1 is the plague receptor on host immune cells

Author

Listed:
  • Patrick Osei-Owusu

    (Argonne National Laboratory
    University of Chicago)

  • Thomas M. Charlton

    (Argonne National Laboratory
    University of Chicago)

  • Hwan Keun Kim

    (Argonne National Laboratory
    University of Chicago)

  • Dominique Missiakas

    (Argonne National Laboratory
    University of Chicago)

  • Olaf Schneewind

    (Argonne National Laboratory
    University of Chicago)

Abstract

The causative agent of plague, Yersinia pestis, uses a type III secretion system to selectively destroy immune cells in humans, thus enabling Y. pestis to reproduce in the bloodstream and be transmitted to new hosts through fleabites. The host factors that are responsible for the selective destruction of immune cells by plague bacteria are unknown. Here we show that LcrV, the needle cap protein of the Y. pestis type III secretion system, binds to the N-formylpeptide receptor (FPR1) on human immune cells to promote the translocation of bacterial effectors. Plague infection in mice is characterized by high mortality; however, Fpr1-deficient mice have increased survival and antibody responses that are protective against plague. We identified FPR1R190W as a candidate resistance allele in humans that protects neutrophils from destruction by the Y. pestis type III secretion system. Thus, FPR1 is a plague receptor on immune cells in both humans and mice, and its absence or mutation provides protection against Y. pestis. Furthermore, plague selection of FPR1 alleles appears to have shaped human immune responses towards other infectious diseases and malignant neoplasms.

Suggested Citation

  • Patrick Osei-Owusu & Thomas M. Charlton & Hwan Keun Kim & Dominique Missiakas & Olaf Schneewind, 2019. "FPR1 is the plague receptor on host immune cells," Nature, Nature, vol. 574(7776), pages 57-62, October.
    • Handle: RePEc:nat:nature:v:574:y:2019:i:7776:d:10.1038_s41586-019-1570-z
    DOI: 10.1038/s41586-019-1570-z
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    Cited by:

    1. Youwen Zhuang & Lei Wang & Jia Guo & Dapeng Sun & Yue Wang & Weiyi Liu & H. Eric Xu & Cheng Zhang, 2022. "Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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