Superoxide anion production during Anaplasma phagocytophila infection.
Anaplasma phagocytophila persists within neutrophils and prevents the respiratory burst by inhibiting gp91(phox). Mutations in gp91(phox) result in chronic granulomatous disease (CGD), which is diagnosed by use of the nitroblue tetrazolium (NBT) and Fc-Oxyburst assays that examine whether cells produce O2-. This study assessed whether the NBT and Fc-Oxyburst assays could detect a respiratory burst during A. phagocytophila infection. O2- production was inhibited in HL-60 cells and neutrophils infected with A. phagocytophila. In a mouse model of A. phagocytophila infection, 15%+/-4% (mean+/-SD) of polymorphonuclear leukocytes from infected mice had an ineffective respiratory burst compared with 1%+/-1% (mean+/-SD) of the neutrophils from uninfected animals. A population of neutrophils that did not produce O2- was also detected in 2 patients with A. phagocytophila infection. These data demonstrate respiratory burst inhibition by A. phagocytophila in vivo and on an individual cell basis by use of assays designed to evaluate CGD.
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. tian.wang@yale.edu
Tian
T
Wang
Stephen E
SE
Malawista
Utpal
U
Pal
Mark
M
Grey
James
J
Meek
Mustafa
M
Akkoyunlu
Venetta
V
Thomas
Erol
E
Fikrig
D000709:Anaplasma / Q000378:metabolism*; D000712:Anaplasmosis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016873:Ehrlichiosis / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016513:Mice, SCID; D009504:Neutrophils / Q000378:metabolism*; D009580:Nitroblue Tetrazolium; D016897:Respiratory Burst; D013481:Superoxides / Q000097:blood / Q000378:metabolism*
D013481:Superoxides; D009580:Nitroblue Tetrazolium