Cutting edge: infection by the agent of human granulocytic ehrlichiosis prevents the respiratory burst by down-regulating gp91phox.
The agent of human granulocytic ehrlichiosis (HGE) is an emerging tick-borne pathogen that resides in neutrophils and can be cultured in a promyelocytic (HL-60) cell line. In response to microbes, polymorphonuclear leukocytes normally activate the NADPH oxidase enzyme complex and generate superoxide anion (O2-). However, HL-60 cells infected with HGE bacteria did not produce O2- upon activation with PMA. RT-PCR demonstrated that HGE organisms inhibited mRNA expression of a single component of NADPH oxidase, gp91phox, and FACS analysis showed that plasma membrane-associated gp91phox protein was reduced on the infected cells. Infection with HGE organisms also decreased gp91phox mRNA levels in splenic neutrophils in a murine model of HGE, demonstrating this phenomenon in vivo. Therefore, HGE bacteria repress the respiratory burst by down-regulating gp91phox, the first direct inhibition of NADPH oxidase by a pathogen.
Banerjee
R
R
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Anguita
J
J
Roos
D
D
Fikrig
E
E
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D018469:Ehrlichia chaffeensis / Q000276:immunology*; D016873:Ehrlichiosis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016897:Respiratory Burst / Q000276:immunology*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013481:Superoxides; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases