Mucosal immunology of HIV infection

Abstract

Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients.

HIV-1 reprograms the migration of macrophages

“…7 In the gastrointestinal tract, infected macrophages induce severe damages to mucosal barriers, resulting in translocation of others pathogens, a hallmark of HIV-1 infection. [9][10][11] Therefore, control of tissue infiltration of HIV-infected macrophages represents a therapeutic challenge. 7,9,12 Although there are no studies investigating whether macrophage migration is modified on HIV-1 infection, several reports have addressed this issue in infected CD4…”

Mucosal Immunity to HIV-1

“…Studies in this model system have identified resting vaginal CD4+ T cells expressing CCR5 (▶ HIV-1 Transmission; Association with Host Genotypes) but negative for activation markers HLA-DR and Ki67, as early targets for infection (Haase 2011). The susceptibility of vaginal CD4+ T cells to infection is also illustrated by the rapid depletion of these cells following intravenous exposure to SIV (Xu et al 2013).…”

“…These studies suggest that both cell-free and cell-associated virions can successfully establish infection through the female reproductive tract. The precise events that allow HIV-1 to traverse the genital epithelium remain controversial but may include transcytosis across intact epithelial cells; transport through gaps between epithelial cells, or through breaches in the epithelial layer; binding and uptake by Langerhans cells in the genital epithelium, followed by transfer of virion particles to T cells; and direct infection of intraepithelial CD4+ T cells (Hladik and McElrath 2008;Xu et al 2013; Fig. 1).…”

“…In rhesus macaques, progestin application increases susceptibility to vaginal SIV transmission, likely by promoting thinning of the vaginal epithelium. However, the effects of progestins on human vaginal epithelial thinning are reportedly less pronounced (Rodriguez-Garcia et al 2013;Xu et al 2013). Several studies have assessed whether use of progestin-based contraceptives affects HIV-1 susceptibility in women.…”

Short Communication: Exploring Antibody Potential as Prophylactic/Therapeutic Strategies for Prevention of Early Mucosal HIV-1 Infection

“…[1][2][3] Various mucosal target cells including antigen-presenting cells (APCs) such as Langerhans cells (LCs), interstitial dendritic cells (iDCs), or plasmacytoid dendritic cells have the capacity to capture antigen, to migrate to draining lymph nodes, and to transfer HIV to surrounding memory CD4 + T cells. [4][5][6][7] Dendritic cells (DCs) play a critical role in HIV transmission by transporting infectious HIV virions without being infected themselves (transfer in trans) or by transferring newly synthesized virus (transfer in cis).…”