Cutting edge: Infection by the agent of human granulocytic ehrlichiosis prevents the respiratory burst by down-regulating gp91(phox1)

The agent of human granulocytic ehrlichiosis (HGE) is an emerging tick-born e pathogen that resides in neutrophils and can be cultured in a promyelocyt ic (HL-60) cell line. In response to microbes, polymorphonuclear leukocytes normally activate the NADPH oxidase enzyme complex and generate superoxide anion (O-2(-)). However, HL-60 cells infected with HGE bacteria did not pr oduce O-2(-) upon activation with PMA, RT-PCR demonstrated that HGE organis ms inhibited mRNA expression of a single component of NADPH oxidase, gp91(p hox) and FAGS analysis showed that plasma membrane-associated gp91(phox) pr otein was reduced on the infected cells. Infection with HGE organisms also decreased gp91(phox) mRNA levels in splenic neutrophils in a murine model o f HGE, demonstrating this phenomenon in vivo. Therefore, HGE bacteria repre ss the respiratory burst by down-regulating gp91(phox), the first direct in hibition of NADPH oxidase by a pathogen.