HIV-1 infection and HIV-1 Tat protein permit the survival and replication of a non-pathogenic trypanosomatid in macrophages through TGF-beta1 production.
Monoxenic trypanosomatids, which usually are non-pathogenic in humans, have been detected in AIDS patients, but the mechanisms underlying the establishment of these protozoa in HIV-1-infected individuals are poorly understood. Here we addressed the role of HIV-1 and the HIV-1 Tat protein in the replication of the monoxenic trypanosomatid Blastocrithidia culicis in HIV-1-infected primary human macrophages. We found that HIV-1 and B. culicis replication augmented almost three times in co-infected macrophages, and that Tat antiserum significantly reduced the exacerbated protozoan growth. Exposure of B. culicis only infected macrophages to Tat protein also resulted in enhanced protozoan proliferation, reaching a twofold increase at 100 ng/mL. Electron microscopy analysis revealed that B. culicis and HIV-1 co-habit the same cells, and showed protozoan dividing forms inside macrophages. Protozoan replication diminished when B. culicis only infected macrophages were treated with Tat protein in the presence of anti-TGF-beta1 antibodies, suggesting a participation of this cytokine in the augmentation of protozoan multiplication. In fact, exogenous TGF-beta1 promoted the trypanosomatid replication in macrophages. Overall, our results suggest that HIV-1 infection deactivates the macrophage microbicidal activity, permitting the survival and multiplication of an otherwise non-pathogenic protozoan in these cells, a process partially mediated by Tat protein, via TGF-beta1 secretion.
Barreto-de-Souza
Victor
V
Laboratório de Imunologia Clínica, Instituto Oswaldo Cruz/FIOCRUZ, RJ, Brazil.
Xavier Medeiros
Thalyta
T
Machado Motta
Maria Cristina
MC
Bou-Habib
Dumith Chequer
DC
Saraiva
Elvira M
EM
D000818:Animals; D015658:HIV Infections / Q000473:pathology*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D014351:Trypanosomatina / Q000187:drug effects* / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000494:pharmacology*
D053773:Transforming Growth Factor beta1; D054322:tat Gene Products, Human Immunodeficiency Virus