title: Role of the Yersinia YopJ protein in suppressing interleukin-8 secretion by human polymorphonuclear leukocytes.
abstract: Polymorphonuclear leukocytes, in addition to their direct bactericidal activities, produce cytokines involved in the activation and regulation of the innate and adaptive immune response to infection. In this study we evaluated the cytokine response of human PMNs following incubation with the pathogenic Yersinia species. Yersinia pestis strains with the pCD1 virulence plasmid, which encodes cytotoxic Yop proteins that are translocated into host cells, stimulated little or no cytokine production compared to pCD1-negative strains. In particular, PMNs incubated with pCD1-negative Y. pestis secreted 1000-fold higher levels of interleukin-8 (IL-8 or CXCL8), a proinflammatory chemokine important for PMN recruitment and activation. Deletion of yopE, -H, -T, -M or ypkA had no effect on pCD1-dependent inhibition, whereas deletion of yopJ resulted in significantly increased IL-8 production. Like Y. pestis, the enteropathogenic Yersinia species inhibited IL-8 secretion by PMNs, and strains lacking the virulence plasmid induced high levels of IL-8. Our results show that virulence plasmid-encoded effector Yops, particularly YopJ, prevent IL-8 secretion by human PMNs. Suppression of the chemotactic IL-8 response by Y. pestis may contribute to the delayed PMN recruitment to the infected lymph node that typifies bubonic plague.
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 905 S. 4th St., Hamilton, Montana 59840, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Spinner
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 905 S. 4th St., Hamilton, Montana 59840, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Hasenkrug
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 905 S. 4th St., Hamilton, Montana 59840, USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Shannon
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 905 S. 4th St., Hamilton, Montana 59840, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 905 S. 4th St., Hamilton, Montana 59840, USA. Electronic address: jhinnebusch@niaid.nih.gov.
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D010957:Plasmids; D037521:Virulence Factors; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D037521:Virulence Factors; C109227:YopP protein, Yersinia
keywords: CXCL8; IL-8; Neutrophil; Plague; Yersinia; YopJ