Monocytes, dendritic cells, and Langerhans cells in human immunodeficiency virus infection

Abstract

Cells of the immune system are the target of infection with HIV. CD4 + T cells latently carry much of the viral burden in the blood and ultimately are depleted by infection with HIV. In contrast, infected tissue macrophages are long-lived and may serve as a viral reservoir. They are productive of relatively greater quantities of viral message RNA and its transcriptional product, infectious virions. Viral production by both cell types is modulated by environmental cytokines, the availability of which may be modified by the virus itself or by abnormally functioning HIV-infected immune cells. Not all susceptible cells are equally infected; although this phenomenon is not well understood, it has been related in vitro to maturation or differentiation. Blood DC and LC, antigen-presenting cells bearing many similarities to cells of the monocyte-macrophage lineage, are susceptible to HIV infection in vitro. Some evidence clearly indicates that, in vivo, epidermal LC may be infected with and productive of HIV and may be depleted or phenotypically altered in the HIV-infected individual. We, and others, have been unable to substantiate these findings by routine techniques used in the identification of HIV-infected macrophages in susceptible tissues, such as the brain, lungs, and lymph nodes (in situ hybridization for HIV-specific mRNA, electron microscopy for typical viral particles, recovery of infectious virus onto target cells, immunohistochemical staining of surface proteins in tissue, and polymerase chain reaction amplification of viral DNA). Evidence for the presence of HIV within the dermis of patients is clear; however, dermis contains a great variety of cell types as well as cells from the peripheral blood. We feel strongly that were the epidermis to harbor virus to any significant degree, it would have been identified by at least some of the methods described earlier. Although it is difficult to reconcile these reported differences, it appears that LC must be infected rarely. LC from lesional and apparently normal skin of HIV-infected individuals do not serve as an important reservoir of infectious HIV. Additionally, the diverse cutaneous manifestations seen in this population cannot be attributed directly to viral presence within the lesions but are more likely to result from the multifacted immunologic disregulation occurring systemically.