Th17 cells in pathogenic simian immunodeficiency virus infection of macaques

Abstract

Purpose of review: We discuss studies on a subset of CD4T cells, designated Th17, and their role in the pathogenesis of human and simian acquired immune deficiency, caused by infection with HIV and simian immunodeficiency virus (SIV), respectively. Most of the Th17 cells are lost within 2 weeks from infection at mucosal sites of SIV-infected macaques and are not replenished over time. Comparison of simian pathogenic and nonpathogenic models of SIV infection suggests that Th17 cells contribute to the pathogenesis of AIDS.

Recent findings: Th17 cells, a recently identified subset of T helper cells, play a major role in both inducing autoimmune disorders and fencing off extracellular pathogens. Several groups have reported that the number of Th17 cells is decreased in the gut of HIV-infected and SIV-infected hosts. The loss of Th17 cells from the mucosal compartment has been associated with the dissemination of Salmonella typhimurium that is normally contained locally by the host immune system. It is believed that microbial translocation sustains immune activation in HIV infection and contributes to AIDS.

Summary: Understanding the mechanisms that lead to disruption of mucosal integrity, viral spread, and chronic immune activation is of crucial importance for the design of efficient vaccines and therapeutic intervention for HIV.

Figure 1. Pathogenic SIV infection in macaques induces depletion of Th17 cells in gut mucosa

Th17 cells are mainly localized in the intestinal mucosa, where they fight extracellular bacteria. Pathogenic SIV infection in macaques results in a strong depletion of Th17 cells and a consequent spread of bacteria from the intestinal lumen to the systemic compartment. Microbial translocation is believed to be responsible for persistent immune activation and progression to AIDS. Elite-controller animals, which naturally contain viral replication, maintain normal levels of Th17 cells in the intestinal mucosa, thus preventing microbial spreading, immune activation and disease onset.