Human Immunodeficiency Virus Infection and Host Defense in the Lungs

Abstract

Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections.

Figure 1

Pulmonary host defense mechanisms.

Figure 2

Tropism of HIV strains for lung cells. Coreceptors determine viral entry into different cell types. Macrophages express CCR5 and CXCR4, whereas T cell lines only express CXCR4. M-tropic strains infect macrophages using CD4 as the main receptor and the coreceptor CCR5. T tropic stains infect T cells using CXCR4 as the coreceptor. The dual tropic strain is able to use either coreceptor and is therefore able to infect both cell types.

Figure 3

Immune reactions to HIV in the alveolar space. The presence of HIV-infected cells, or free virus, in lung tissue stimulates an adaptive immune response and the recruitment of HIV-specific cytotoxic T cells (CTLs). These CTLs accumulate in the alveolar space and release pro-inflammatory cytokines that further activate alveolar macrophages to release additional cytokines leading to further inflammatory cell recruitment. When infected with HIV, alveolar macrophages are compromised in binding and recognizing pathogen and the level of CD4 T cells is decreased.