A critical role of formyl peptide receptors in host defense against Escherichia coli

Meihua Zhang, Ji Liang Gao, Keqiang Chen, Teizo Yoshimura, Weiwei Liang, Wanghua Gong, Xiaoqing Li, Jiaqiang Huang, David H. McDermott, Philip M. Murphy, Xietong Wang, Ji Ming Wang

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Abstract

Formyl peptide receptors (FPRs, mouse Fprs) belong to the G protein-coupled receptor superfamily and mediate phagocyte migration in response to bacteria- and host-derived chemoattractants; however, knowledge about their in vivo roles in bacterial pathogenesis is limited. In this study, we investigated the role of Fpr1 and Fpr2 in host defense against Escherichia coli infection. In vitro, we found that supernatants from E. coli cultures induced chemotaxis of wild-type (WT) mouse bone marrow-derived neutrophils and that the activity was significantly reduced in cells genetically deficient in either Fpr1 or Fpr2 and was almost absent in cells lacking both receptors. Consistent with this, E. coli supernatants induced chemotaxis and MAPK phosphorylation in HEK293 cells expressing either recombinant Fpr1 or Fpr2 but not untransfected parental cells. WT bone marrow -derived neutrophils could actively phagocytose and kill E. coli, whereas both activities were diminished in cells lacking Fpr1 or Fpr2; again, an additive effect was observed in cells lacking both receptors. In vivo, Fpr1 and Fpr2 deficiency resulted in reduced recruitment of neutrophils in the liver and peritoneal cavity of mice infected with inactivated E. coli. Moreover, Fpr12/2 and Fpr2-/- mice had significantly increased mortality compared with WT mice after i.p. challenge with a virulent E. coli clinical isolate. These results indicate a critical role of Fprs in host defense against E. coli infection.

Original languageEnglish
Pages (from-to)2464-2473
Number of pages10
JournalJournal of Immunology
Volume204
Issue number9
DOIs
Publication statusPublished - May 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Zhang, M., Gao, J. L., Chen, K., Yoshimura, T., Liang, W., Gong, W., Li, X., Huang, J., McDermott, D. H., Murphy, P. M., Wang, X., & Wang, J. M. (2020). A critical role of formyl peptide receptors in host defense against Escherichia coli. Journal of Immunology, 204(9), 2464-2473. https://doi.org/10.4049/jimmunol.1900430