CXCR2 blockade influences Anaplasma phagocytophilum propagation but not histopathology in the mouse model of human granulocytic anaplasmosis.
Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils and causes human granulocytic anaplasmosis. Infection induces neutrophil secretion of interleukin-8 or murine homologs and perpetuates infection by recruiting susceptible neutrophils. We hypothesized that antibody blockade of CXCR2 would decrease A. phagocytophilum tissue load by interrupting neutrophil recruitment but would not influence murine hepatic pathology. C3H-scid mice were treated with CXCR2 antiserum or control prior to or on day 14 after infection. Quantitative PCR and immunohistochemistry for A. phagocytophilum were performed and severity of liver histopathology was ranked. Control mice had more infected cells in tissues than the anti-CXCR2-treated group. The histopathological rank was not different between treated and control animals. Infected cells of control mice clustered in tissue more than in treated mice. The results support the hypothesis of bacterial propagation through chemokine induction and confirm that tissue injury is unrelated to A. phagocytophilum tissue load.
Scorpio
Diana G
DG
Department of Comparative Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Akkoyunlu
Mustafa
M
Fikrig
Erol
E
Dumler
J Stephen
JS
D041081:Anaplasma phagocytophilum / Q000254:growth & development* / Q000472:pathogenicity; D000712:Anaplasmosis / Q000209:etiology* / Q000382:microbiology / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D006098:Granulocytes / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009504:Neutrophils / Q000382:microbiology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
D007106:Immune Sera; D023063:Receptors, Interleukin-8B