Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis.

Abstract

Transforming growth factor I8 (TGF-1) has potent down-regulating effects on macrophages and is thus capable of influencing the fate of intramacrophage parasites, including leishmanias. We report the development of a mouse model for the study of the human pathogen Leishmania braziliensis and demonstrate, both in vitro and in vivo, a key regulatory role for TGF-fi in the pathogenesis of infection with this parasite. Recombinant TGF-fi added to cultures of murine peritoneal macrophages led to increased intracellular L. braziliensis replication, whereas addition of neutralizing anti-TGF-fi monoclonal antibody decreased levels of infection.Macrophages infected with L. braziliensis produced biologically active TGF-(3, with a direct correlation between amounts of TGF-13 induced by two parasite isolates and their relative virulence. In vivo, treatment with recombinant TGF-fi rendered avirulent parasites virulent and activated latent L. braziliensis infection. Activation of parasite replication was observed in mice which had been infected with L. braziliensis 15 weeks previously but had not developed lesions or had healed lesions, depending on the parasite isolate used to infect the mice. The exacerbation of L. braziliensis infection in vivo was associated with an increase of interleukin 10 mRNA in the draining lymph node. These results demonstrate that TGF-13 is able to alter the course of in vitro and in vivo infections with L.

Transforming growth factor-β expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis of retinochoroiditis

“…Elevated levels of active TGF-b were produced by spleen cells from mice infected with Trypanosoma cruzi [29] and by normal mouse peritonial macrophages infected with Leishmania braziliensis [30]. However, there are no studies on TGF-b secretion or effects of TGF-b on T. gondii replication in either retinal cells or cells of the immune system.…”

Evaluation of TNF-α, IL-4, and IL-10 and parasite density in spleen and liver ofL. (L.) chagasinaturally infected dogs

“…This expression was quantitatively similar in both asymptomatic and symptomatic dogs (Manna et al, 2006). IL-10 has been indicated as one of the mainsuppressing cytokines of the protective immune response, both in murine models and in humans with VL (Barral et al, 1993;Bacellar et al, 2000). However, more recently, studies have indicated that the anti-inflammatory effects of IL-10 may limit the side effect caused by an excessive inflammatory response, while also interfering with the process of parasite elimination (Trinchieri, 2007).…”

B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniases

“…Predominance of Th1 cytokines like IFN-γ, IL-12, IL-2 and TNF-α over Th2 cytokines, IL-4, IL-5 IL-10 and TGF-β, is correlated in mice to the resistance profile against Leishmania infection (Belosevic et al 1989, Chatelain et al 1992, Lezama-Davila et al 1992, Barral et al 1993. Imunological studies in humans demonstrated a combination of Th1 and Th2 cytokines with predominance of Th1 in MCL, Th2 predominate in DCL and predominance of Th1 profile in LCL patients , Castes et al 1993.…”

“…It seems that B cells are important to induce anti-Leishmania CD4 + Th1 cells and DTH reaction, in the resistant mouse strain, and take part in the humoral response development in susceptible animals (Scott & Farrell 1982, Scott et al 1986). Predominance of Th1 cytokines like IFN-γ, IL-12, IL-2 and TNF-α over Th2 cytokines, IL-4, IL-5 IL-10 and TGF-β, is correlated in mice to the resistance profile against Leishmania infection (Belosevic et al 1989, Chatelain et al 1992, Lezama-Davila et al 1992, Barral et al 1993. Imunological studies in humans demonstrated a combination of Th1 and Th2 cytokines with predominance of Th1 in MCL, Th2 predominate in DCL and predominance of Th1 profile in LCL patients , Castes et al 1993.…”