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FPR1 is the plague receptor on host immune cells

The plague agent, Yersinia pestis, employs a type III secretion system (T3SS) to selectively destroy human immune cells, thereby enabling its replication in the bloodstream and transmission to new hosts via fleabite. The host factors responsible for the selective destruction of immune cells by plagu...

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Autores principales: Osei-Owusu, Patrick, Charlton, Thomas M., Kim, Hwan Keun, Missiakas, Dominique, Schneewind, Olaf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776691/
https://www.ncbi.nlm.nih.gov/pubmed/31534221
http://dx.doi.org/10.1038/s41586-019-1570-z
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author Osei-Owusu, Patrick
Charlton, Thomas M.
Kim, Hwan Keun
Missiakas, Dominique
Schneewind, Olaf
author_facet Osei-Owusu, Patrick
Charlton, Thomas M.
Kim, Hwan Keun
Missiakas, Dominique
Schneewind, Olaf
author_sort Osei-Owusu, Patrick
collection PubMed
description The plague agent, Yersinia pestis, employs a type III secretion system (T3SS) to selectively destroy human immune cells, thereby enabling its replication in the bloodstream and transmission to new hosts via fleabite. The host factors responsible for the selective destruction of immune cells by plague bacteria were not known. Here we show that LcrV, the needle cap protein of the Y. pestis T3SS, binds 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 N-formylpeptide receptor deficient animals exhibit increased survival and plague-protective antibody responses. We identified FPR1 p.R190W as a candidate human resistance allele that protects neutrophils from Y. pestis T3SS. These findings reveal the plague receptor on immune cells and show that FPR1 mutations provide for plague survival, which appears to have shaped human immune responses towards other infectious diseases and malignant neoplasms.
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spelling pubmed-67766912020-03-18 FPR1 is the plague receptor on host immune cells Osei-Owusu, Patrick Charlton, Thomas M. Kim, Hwan Keun Missiakas, Dominique Schneewind, Olaf Nature Article The plague agent, Yersinia pestis, employs a type III secretion system (T3SS) to selectively destroy human immune cells, thereby enabling its replication in the bloodstream and transmission to new hosts via fleabite. The host factors responsible for the selective destruction of immune cells by plague bacteria were not known. Here we show that LcrV, the needle cap protein of the Y. pestis T3SS, binds 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 N-formylpeptide receptor deficient animals exhibit increased survival and plague-protective antibody responses. We identified FPR1 p.R190W as a candidate human resistance allele that protects neutrophils from Y. pestis T3SS. These findings reveal the plague receptor on immune cells and show that FPR1 mutations provide for plague survival, which appears to have shaped human immune responses towards other infectious diseases and malignant neoplasms. 2019-09-18 2019-10 /pmc/articles/PMC6776691/ /pubmed/31534221 http://dx.doi.org/10.1038/s41586-019-1570-z Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Osei-Owusu, Patrick
Charlton, Thomas M.
Kim, Hwan Keun
Missiakas, Dominique
Schneewind, Olaf
FPR1 is the plague receptor on host immune cells
title FPR1 is the plague receptor on host immune cells
title_full FPR1 is the plague receptor on host immune cells
title_fullStr FPR1 is the plague receptor on host immune cells
title_full_unstemmed FPR1 is the plague receptor on host immune cells
title_short FPR1 is the plague receptor on host immune cells
title_sort fpr1 is the plague receptor on host immune cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776691/
https://www.ncbi.nlm.nih.gov/pubmed/31534221
http://dx.doi.org/10.1038/s41586-019-1570-z
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