Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type 1-infectedmonocytes/macrophages in vitro and in vivo

The role of human immunodeficiency virus type 1 (HIV-1) infection on the ab ility of human monocytes/macrophages to phagocytose Mycobacterium avium com plex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage co lony-stimulating factor (GM-CSF) on this function were investigated, By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was f ound to impair the ability of monocyte-derived macrophages to phagocytose M AC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosi s was not altered by exposure to a mutant form of GM-CSF (E21R) binding onl y to the alpha chain of the GM-CSF receptor, suggesting that signaling by G M-CSF that leads to augmentation of phagocytosis is via the beta chain of t he receptor. In a patient with AIDS and disseminated multidrug-resistant MA C infection, GM-CSF treatment improved phagocytosis of MAC by peripheral bl ood monocytes and reduced bacteremia, These results imply that GM-CSF thera py may be useful in restoring antimycobacterial function by human monocytes /macrophages.