T‐bet, GATA‐3, and Foxp3 Expression and Th1/Th2 Cytokine Production in the Clinical Outcome of Human Infection withLeishmania (Viannia)Species

Abstract

Background T cell differentiation determines susceptibility and resistance to experimental cutaneous leishmaniasis, yet mixed T1/Th2 responses characterize the clinical spectrum of human infection with Leishmania Viannia species. Materials and Methods To discern the inter-relationship of T cell differentiation and outcome of human infection, we examined factors that regulate T cell differentiation and Th1/Th2 cytokine responses in asymptomatic infection, active and historical chronic and recurrent cutaneous leishmaniasis. T-bet, GATA-3, Foxp3 and cytokine gene expression were quantified by real time PCR, and correlated with IL-2, IFN-γ, TNF-α, IL-4, IL-13, IL-10 secretion during in vitro response to live L. panamensis. Results Higher GATA-3 than T-bet expression occurred throughout the 15 days of co-culture with promastigotes, however neither transcription nor secretion of IL-4 was detected. Sustained, inverse correlation between GATA-3 expression and secretion of proinflammatory cytokines IFN-γ and TNF-α was observed in asymptomatic infection. In contrast, higher T-bet expression and T-bet:GATA-3 ratio characterized active recurrent disease. Down-regulation of T-bet and GATA-3 expression and increased IL-2 secretion compared to control was directly correlated with Foxp3 expression and IL-13 secretion in chronic disease. Conclusions Regulation of the inflammatory response rather than biased Th1/Th2 response distinguished asymptomatic and recalcitrant outcomes of infection with Leishmnania Viannia species.

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