The mucosal barrier and immune activation in HIV pathogenesis

Abstract

Purpose of review: Significant gastrointestinal pathology occurs in progressive HIV and simian immunodeficiency virus (SIV) infections. This review will examine the relationship between the detrimental events to the gastrointestinal tract during the acute phase of infection and disease progression through the chronic phase and, ultimately, AIDS.

Recent findings: Gastrointestinal tract CD4 T cells are dramatically depleted in acutely HIV-infected humans and SIV-infected rhesus macaques, sooty mangabeys, and African green monkeys. In addition HIV infection of humans and SIV-infection of rhesus macaques are characterized by enteropathy and increased intestinal permeability. While SIV-infected rhesus macaques and HIV-infected humans manifest chronic and systemic immune activation and microbial translocation, and progress to chronic infection and AIDS, however, SIV-infected sooty mangabeys and African green monkeys do not.

Summary: Recent studies have increased our understanding of the mechanisms relating structural and immunological damage to the gastrointestinal tract during the acute phase of HIV/SIV infection to immune activation and disease progression in the chronic phase.

Figure 1. Relative depletion of initial gastrointestinal tract CD4 T cells in progressive and nonprogressive lentiviral infection

Depletion of gastrointestinal tract CD4 T cells, relative to the preinfection frequency, during the acute and chronic phases of HIV in humans (black line) and SIV infection in Rhesus macaques (dashed line), sooty mangabeys (dotted line line), and African green monkeys (gray line). Frequencies of T cells that are CD4⁺ prior to infection and after the acute phase are listed. Graphs are based upon published data. Neither African green monkeys nor sooty mangabeys (naturally infected animals that do not progress to AIDS) are as dramatically depleted of their initial gastrointestinal tract CD4 T cell populations during the acute phase of infection as SIV-infected rhesus macaques or HIV-infected humans. Moreover, progressive depletion of gastrointestinal tract CD4 T cells does not seem to occur in SIV-infected sooty mangabeys during the chronic phase of infection and SIV-infected African green monkeys actually reconstitute CD4 T cells during the chronic phase.