Subversion of monocyte functions by Coxiella burnetii: Impairment of the cross-talk between alpha(v)beta(3) integrin and CR3

Several intracellular pathogens exploit macrophages as a niche for survival and replication,The success of this strategy-requires the subversion or th e avoidance of microbicidal functions of macrophages, Coxiella burnetii, th e agent of Q fever, is a strictly intracellular bacterium that multiplies i n myeloid cells, The survival of C. burnetii may depend on the selective us e of macrophage receptors, Virulent C. burnetii organisms were poorly Inter nalized but survived successfully in human monocytes, whereas avirulent var iants were efficiently phagocytosed but mere also rapidly eliminated, The u ptake of avirulent organisms was mediated by leukocyte response integrin (a lpha(v)beta(3) integrin) and CR3 (alpha(M)beta(2) integrin), as demonstrate d by using specific Abs and RGD sequence-containing peptides, The phagocyti c efficiency of CR3 depends on its activation via alpha(v)beta(3) integrin and integrin-associated protein, Indeed, CR3-mediated phagocytosis of aviru lent C, burnetii was abrogated in macrophages from integrin-associated prot ein(-/-); mice. In contrast, the internalization of virulent C.burnetii org anisms involved the engagement of alpha(v)beta(3) integrin but not that of CR3, The pretreatment of monocytes with virulent C, burnetii organisms prev ented the CR3-mediated phagocytosis of zymosan particles and CR3 activation assessed by the expression of the 24 neo epitope. We conclude that the vir ulence of C, burnetii is associated with the engagement of alpha(v)beta(3) integrin and the impairment of CR3 activity which probably results from unc oupling alpha(v)beta(3) integrin from integrin-associated protein, This stu dy describes a strategy not previously reported of phagocytosis modulation by intracellular pathogens.