Publications & Reports

Defective phagocytosis by human monocyte/macrophages following HIV-1 infection: underlying mechanisms and modulation by adjunctive cytokine therapy.

Kedzierska K, Azzam R, Ellery P, Mak J, Jaworowski A, Crowe SM
AIDS Pathogenesis Research Unit, Macfarlane Burnet Institute for Medical Research and Public Health. Melbourne, VIC 3181, Australia.


Defective immunological function of cells of the macrophage lineage contributes considerably to the pathogenesis of HIV-1 infection. Impairment of phagocytosis of opportunistic pathogens such as Mycobacterium avium complex (MAC), Pneumocystis carinii, Toxoplasma gondii or Candida albicans by peripheral blood monocytes, tissue macrophages and monocyte-derived macrophages following in vivo and in vitro HIV-1 infection is well documented.

The development of opportunistic infections due to these pathogens in HIV-infected individuals at late stages of disease is attributed to defective monocyte/macrophage function. The mechanisms whereby HIV-1 impairs phagocytosis are not well known. A number of phagocytic receptors normally mediate engulfment of specific opportunistic pathogens by cells of macrophage lineage; distinct mechanisms are triggered by pathogen-receptor binding to promote cytoskeletal rearrangements and engulfment.

This review focuses on the signalling events occurring during Fcgamma receptor- and complement receptor-mediated phagocytosis, and considers the mechanisms by which HIV-1 inhibits those signalling events. Since macrophage function is enhanced by cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma), the use of these immunomodulators is of potential interest as adjunctive immunotherapy in immunosuppressed individuals. In this review we present examples of clinical applications of GM-CSF and IFN-gamma therapy for the treatment of opportunistic infections in HIV-infected individuals receiving antiretroviral drugs.


  • Journal: Journal of Clinical Virology
  • Published: 01/02/2003
  • Volume: 26
  • Issue: 2
  • Pagination: 247-263

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