Coxiella burnetii avoids macrophage phagocytosis by interfering with spatial distribution of complement receptor 3

Phagocytosis is a highly localized event requiring the formation of spatially and temporally restricted signals. Numerous micro-organisms have taken advantage of this property to invade host cells. Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that has developed a survival strategy in macrophages based on subversion of receptor-mediated phago-cytosis. The uptake of C. burnetii is mediated by v3 integrin and is restricted by impaired cross-talk of v3 integrin and complement receptor 3 (CR3) (CD11b/CD18). In this study, we showed that CR3 molecules remained outside the pseudopodal extensions induced by C. burnetii in THP-1 monocytes, although v3 integrin was present in the pseudopods. Chemoattractants such as RANTES restored CR3 localization to the front of pseudopodal extensions and increased C. burnetii phagocytosis, dem-onstrating that the localization of CR3 is critical for bacterial uptake. In addition, monocyte activation due to the expression of HIV-1 Nef protein also restored CR3-mediated phagocytosis of C. burnetii by allowing CR3 redistribution toward bacterial-induced pseudopods. The redistribution of CR3 and increased C. burnetii phagocytosis in THP-1 cells stimulated by RANTES or expressing Nef were associated with the inhibition of intracellular replication of C. burnetii. Hence, the localization of CR3 is critical for bacterial phagocytosis and also for the control of bacterial replication. This study describes a nonpreviously reported strategy of phagocytosis subversion by intracellular pathogens based on altered localization of monocyte receptors. The Journal of Immunology, 2003, 170: 4217–4225. Coxiella burnetii is an obligate intracellular microorganismclassified in the subdivision of Proteobacteria (1). Itssurvival strategy in monocytes/macrophages is based o