Exploitation of interleukin-8-induced neutrophil chemotaxis by the agent of human granulocytic ehrlichiosis

The agent of human granulocytic ehrlichiosis (HGE) is an obligate intracell ular bacterium with a tropism for neutrophils; however, the mechanisms of b acterial dissemination are not yet understood. Interleukin-8 (IL-8) is a ch emokine that induces neutrophil migration to sites of infection for host de fense against pathogens. We now show that HGE bacteria, and the HGE-44 prot ein, induce IL-8 secretion in a promyelocytic (HL-60) cell line that has be en differentiated along the neutrophil lineage with retinoic acid and in ne utrophils. Infected HL-60 cells also demonstrate upregulation of CXCR2, an IL-8 receptor, but not CXCR1. Human neutrophils migrate towards Ehrlichia s p.-infected cells in a chemotaxis chamber assay, and this movement can be b locked with antibodies to IL-8. Finally, immunocompetent and severe combine d immunodeficient mice administered CXCR2 antisera, and CXCR2(-/-) mice tha t lack the human IL-8 receptor homologue, are much less susceptible to gran ulocytic ehrlichiosis than are control animals. These results demonstrate t hat HGE bacteria induce IL-8 production by host cells and, paradoxically, a ppear to exploit this chemokine to enhance infection.