Exploitation of interleukin-8-induced neutrophil chemotaxis by the agent of human granulocytic ehrlichiosis.
The agent of human granulocytic ehrlichiosis (HGE) is an obligate intracellular bacterium with a tropism for neutrophils; however, the mechanisms of bacterial dissemination are not yet understood. Interleukin-8 (IL-8) is a chemokine that induces neutrophil migration to sites of infection for host defense against pathogens. We now show that HGE bacteria, and the HGE-44 protein, induce IL-8 secretion in a promyelocytic (HL-60) cell line that has been differentiated along the neutrophil lineage with retinoic acid and in neutrophils. Infected HL-60 cells also demonstrate upregulation of CXCR2, an IL-8 receptor, but not CXCR1. Human neutrophils migrate towards Ehrlichia sp.-infected cells in a chemotaxis chamber assay, and this movement can be blocked with antibodies to IL-8. Finally, immunocompetent and severe combined immunodeficient mice administered CXCR2 antisera, and CXCR2(-/-) mice that lack the human IL-8 receptor homologue, are much less susceptible to granulocytic ehrlichiosis than are control animals. These results demonstrate that HGE bacteria induce IL-8 production by host cells and, paradoxically, appear to exploit this chemokine to enhance infection.
Akkoyunlu
M
M
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Malawista
S E
SE
Anguita
J
J
Fikrig
E
E
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D004536:Ehrlichia / Q000276:immunology*; D016873:Ehrlichiosis / Q000276:immunology* / Q000382:microbiology; D006098:Granulocytes; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D023063:Receptors, Interleukin-8B / Q000276:immunology / Q000378:metabolism; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000942:Antigens, Bacterial; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B