Abstract
BackgroundSeveral factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to determine whether T. cruzi modifies HIV infection of the placenta at the tissue or cellular level.ResultsSimple and double infections were carried out on a placental histoculture system (chorionic villi isolated from term placentas from HIV and Chagas negative mothers) and on the choriocarcinoma BeWo cell line. Trypomastigotes of T. cruzi (VD lethal strain), either purified from mouse blood or from Vero cell cultures, 24 h-supernatants of blood and cellular trypomastigotes, and the VSV-G pseudotyped HIV-1 reporter virus were used for the coinfections. Viral transduction was evaluated by quantification of luciferase activity. Coinfection with whole trypomastigotes, either from mouse blood or from cell cultures, decreased viral pseudotype luciferase activity in placental histocultures. Similar results were obtained from BeWo cells. Supernatants of stimulated histocultures were used for the simultaneous determination of 29 cytokines and chemokines with the Luminex technology. In histocultures infected with trypomastigotes, as well as in coinfected tissues, IL-6, IL-8, IP-10 and MCP-1 production was significantly lower than in controls or HIV-1 transducted tissue. A similar decrease was observed in histocultures treated with 24 h-supernatants of blood trypomastigotes, but not in coinfected tissues.ConclusionOur results demonstrated that the presence of an intracellular pathogen, such as T. cruzi, is able to impair HIV-1 transduction in an in vitro system of human placental histoculture. Direct effects of the parasite on cellular structures as well as on cellular/viral proteins essential for HIV-1 replication might influence viral transduction in this model. Nonetheless, additional mechanisms including modulation of cytokines/chemokines at placental level could not be excluded in the inhibition observed. Further experiments need to be conducted in order to elucidate the mechanism(s) involved in this phenomenon. Therefore, coinfection with T. cruzi may have a deleterious effect on HIV-1 transduction and thus could play an important role in viral outcome at the placental level.
Highlights
Several factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from human immunodeficiency virus type 1 (HIV-1) positive mothers with other pathogens
Coinfection with T. cruzi may have a deleterious effect on HIV-1 transduction and could play an important role in viral outcome at the placental level
A recent study demonstrated that placental explants from HIV-1 positive treated women secreted higher levels of leukemia inhibitory factor (LIF), interleukin (IL)-16, and regulated upon activation of normal T cells expressed and secreted (RANTES), soluble factors that inhibit HIV replication, and lower levels of TNF-α and IL-8, proinflammatory factors known as stimulators of viral replication [13]
Summary
Several factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) occurs mainly when the newborn comes in contact with infected secretions of the mother during birth, though HIV-1 can be transmitted through breastfeeding and in utero [1]. Studies performed in large cohorts with a follow-up of 8 years have shown that in utero transmission may still occur before therapy is initiated or effective [6]. This type of transmission seems to be a relevant way of MTCT even when efficient antiretroviral treatment and avoiding breastfeeding are being successfully performed. A recent study demonstrated that placental explants from HIV-1 positive treated women secreted higher levels of leukemia inhibitory factor (LIF), interleukin (IL)-16, and regulated upon activation of normal T cells expressed and secreted (RANTES), soluble factors that inhibit HIV replication, and lower levels of TNF-α and IL-8, proinflammatory factors known as stimulators of viral replication [13]
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