Cutting edge: Infection by the agent of human granulocytic ehrlichiosis prevents the respiratory burst by down-regulating gp91(phox 1)

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, gp91(phox), and FACS analysis showed that plasma membrane-associated gp91(phox) protein was reduced on the infected cells. Infection with HGE organisms also decreased gp91(phox) 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 gp91(phox), the first direct inhibition of NADPH oxidase by a pathogen.