HIV‐1 Inhibits Leishmania‐lnduced Cell Proliferation but not Production of Interleukin‐6 and Tumour Necrosis Factor Alpha

Abstract

The immune response of normal human peripheral blood mononuclear cells (PBMC) after stimulation with human immunodeficiency virus-1 (HIV-1) antigens plus Leishmania donovani promastigotes in vitro was investigated. HIV-1-antigen stimulation of PBMC did not induce the intracellular accumulation of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma). However, cells stimulated with L. donovani antigens exhibited the production of IL-6 and TNF-alpha, but not IFN-gamma. Furthermore, co-stimulation of PBMC with HIV-1 antigen plus L. donovani resulted in the intracellular accumulation of IL-6 and TNF-alpha comparable to that of cells that were activated with L. donovani antigen alone. Heat-inactivated HIV-1 antigen did not appear to induce or suppress cytokine production by PBMC. However, the same HIV antigens did suppress L. donovani-induced proliferation as well as PPD-induced proliferation in a dose-dependent fashion. Elevated levels of serum cytokines have been demonstrated in patients with HIV infection indicating their role in the pathogenesis of HIV-associated immunosuppression. The results may partially support the idea that the abnormally increased cytokine levels in the sera of HIV-infected subjects is due to the various opportunistic pathogens that these patients contract, rather than a response to HIV antigens. As cytokines have been shown to up-regulate HIV replication, the data suggest a role for opportunistic infections in cytokine-induced transactivation of HIV-1 and disease progression.

Human immunodeficiency virus and leishmaniasis

“…[77] A vicious circle is established whereby the protozoan parasite Leishmania induces a more robust HIV-1 production and the virus mediates a greater parasitic replication. Indeed, it has been shown that HIV-1 infection increases the risk of developing VL by 100 to 2,300 times in areas of endemicity, reduces the likelihood of a therapeutic response and greatly increases the probability of relapse.…”

“…In individuals with nonfunctional T-lymphocytes, such as in HIV-infected patients, Leishmania infection becomes increasingly problematic. [77]…”

“…[778081] In addition, immunological disturbances caused by HIV are particularly favorable for the uncontrolled multiplication of the parasite.…”

The Relationship between Leishmaniasis and AIDS: the Second 10 Years

“…It has been confirmed that HIV-1 inhibits the proliferative response to L. donovani (269); this reduced cellular response might be because the known inductive signal for gamma interferon (IFN-␥) is lacking or could be due to the direct influence of anti-inflammatory Th2 cytokines. Wolday et al (272) confirmed that HIV-1 can modulate in vitro and ex vivo cytokine production in response to Leishmania; the addition of HIV-1 to cultures decreased IFN-␥, IL-12, and IL-18 production and increased IL-4 and IL-10 production in response to Leishmania by peripheral blood monocytic cells from healthy donors, while cells from HIV-1-infected and coinfected patients failed to secrete IFN-␥ in response to Leishmania.…”

“…Early after the appearance and report of the first cases of Leishmania-HIV coinfection, it was evident that the presence of both pathogens concomitantly in the same host cell (the macrophage) might have enhanced reciprocal effects that influence the expression and multiplication of either one or both pathogens (36,269). It is thought that the parasite infection found concurrently with HIV induces chronic immune activation, and therefore an increased HIV load and accelerated progression of AIDS (27), whereas immunological disturbances caused by HIV are particularly favorable for the uncontrolled multiplication of the parasite.…”