Chapter 7 - Gastrointestinal Immunity in Natural Hosts of Simian Immunodeficiency Virus

Abstract

In pathogenic human immunodeficiency virus infection of humans and simian immunodeficiency virus (SIV) infection of Asian macaques, so-called non-natural host species, generalized immune activation is closely associated with disease progression. This immune activation is partially driven by the translocation of microbial products from the gastrointestinal (GI) tract into the systemic circulation as a result of the breakdown of the structural and immunological barrier of the intestine. In contrast, natural host species of SIV, such as sooty mangabeys and African green monkeys, maintain healthy GI tract physiology. Although natural hosts typically experience some CD4 T-cell depletion in the GI tract during acute infection, they have evolved a CD4− population of T cells that remain uninfected by SIV throughout infection; these CD4− T cells can maintain effector functions normally associated with CD4+ T cells. These species are able to avoid the pathogenic effects of CD4 depletion, including limited chronic immune activation in the mucosa, maintenance of interleukin-17 production, maintenance of the structural and immunological barriers of the GI tract, and thus avoidance of microbial translocation and subsequent immune activation. The differential pathology within the GI tract in natural and non-natural hosts of SIV may underlie the ability of natural host species to avoid disease progression.