Granulocyte‐Macrophage Colony‐Stimulating Factor Augments Phagocytosis ofMycobacterium aviumComplex by Human Immunodeficiency Virus Type 1–Infected Monocytes/Macrophages In Vitro and In Vivo

Abstract

The role of human immunodeficiency virus type 1 (HIV-1) infection on the ability of human monocytes/macrophages to phagocytose Mycobacterium avium complex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on this function were investigated. By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was found to impair the ability of monocyte-derived macrophages to phagocytose MAC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosis was not altered by exposure to a mutant form of GM-CSF (E21R) binding only to the alpha chain of the GM-CSF receptor, suggesting that signaling by GM-CSF that leads to augmentation of phagocytosis is via the beta chain of the receptor. In a patient with AIDS and disseminated multidrug-resistant MAC infection, GM-CSF treatment improved phagocytosis of MAC by peripheral blood monocytes and reduced bacteremia. These results imply that GM-CSF therapy may be useful in restoring antimycobacterial function by human monocytes/macrophages.

HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup

“…Interestingly, it was previously observed that HIV-1 infection of MDMs decreased phagocytosis of M. avium by B40% (ref. 28). In agreement with this observation, we found that Tat, but not Tat-W11Y, inhibited phagocytosis of M. avium by B30% (Fig.…”

HIV-1 Down-Modulates γ Signaling Chain of FcγR in Human Macrophages: A Possible Mechanism for Inhibition of Phagocytosis

“…A number of monocyte/ macrophage functions are impaired following HIV-1 infection in vivo and in vitro, including chemotaxis (1, 2), phagocytosis (3)(4)(5), intracellular killing (3), and cytokine production (reviewed in Ref. 6).…”

“…Most studies to date have examined these pathways in murine macrophages or cell lines transfected with Fc␥R (22)(23)(24)(25)(26)(27). Following clustering of Fc␥Rs, tyrosine kinases from the Src family associated with ␥-chain of Fc␥R (including Hck and Lyn) are activated (28,29), leading to a rapid and transient phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) 4 present on the ␥ signaling subunits associated with Fc␥RI and Fc␥RIII or on the cytoplasmic domain of Fc␥RII (30). Phosphorylation of ITAMs create docking sites for Syk, which is subsequently activated by phosphorylation (27,31).…”

Immunotherapeutic effects of recombinant adenovirus encoding granulocyte–macrophage colony-stimulating factor in experimental pulmonary tuberculosis

“…These preclinical results offer an alternative for future immunotherapeutic trials in high-risk individuals preventing reactivation of LTB, such as patients with rheumatological diseases treated with anti-TNF-a therapy [49], or HIV/AIDS patients who can develop TB after primary infection or after LTB reactivation. However, this therapeutic approach in HIV infection should be taken with some caution, considering that some studies have shown an increase of viral replication in HIV-infected patients due to higher immune cell activation induced by GM-CSF [50], while others report beneficial therapeutic effects induced by this cytokine [51].…”