FPR1 is the plague receptor on host immune cells.
Nature
; 574(7776): 57-62, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31534221
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peste
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Yersinia pestis
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Receptores de Formil Peptídeo
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Macrófagos
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Neutrófilos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article