HIV-1 infection of mononuclear phagocytic cells: the case for bacterial innate immune deficiency in AIDS

Abstract

HIV-1 infection of mononuclear phagocytic cells, comprising monocytes, macrophages, and dendritic cells, has been the subject of extensive research over the past 20 years. The roles of mononuclear phagocytic cells in transmission of HIV-1 infection and as reservoirs of actively replicating virus have received particular attention. Experimental data have also accumulated about the effects of HIV-1 on the physiological function of mononuclear phagocytic cells, particularly their role in innate immunity to bacteria. The effects of HIV-1 on bacterial innate immune responses by mononuclear phagocytic cells are discussed here together with reports of direct interactions between HIV-encoded products and bacterial innate immune signalling pathways. These reports demonstrate mechanisms for HIV-mediated disruption of innate immune responses by mononuclear phagocytic cells that could provide novel therapeutic targets in HIV-infected patients. The clinical urgency is highlighted by greatly increased risk of invasive bacterial disease in this population, even in the era of highly active antiretroviral therapy. HIV-mediated injury to bacterial innate immunity provides an experimental paradigm that could broaden our overall understanding of innate immunity and be used to study responses to pathogens other than bacteria.