RESUMEN
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 interrelationship 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 polymerase chain reaction and correlated with interleukin 2, interferon gamma, tumor necrosis factor alpha, interleukin 4, interleukin 13, and interleukin 10 secretion during in vitro response to live Leishmania panamensis. RESULTS: Higher GATA-3 expression than T-bet expression occurred throughout the 15 days of coculture with promastigotes; however, neither transcription nor secretion of interleukin 4 was detected. A sustained inverse correlation between GATA-3 expression and secretion of proinflammatory cytokines interferon gamma and tumor necrosis factor alpha was observed in asymptomatic infection. In contrast, higher T-bet expression and a higher ratio of T-bet to GATA-3 characterized active recurrent disease. Down-regulation of T-bet and GATA-3 expression and increased interleukin 2 secretion, compared with control subjects, was directly correlated with Foxp3 expression and interleukin 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.
Asunto(s)
Citocinas/metabolismo , Factores de Transcripción Forkhead/biosíntesis , Factor de Transcripción GATA3/biosíntesis , Leishmaniasis/inmunología , Proteínas de Dominio T Box/biosíntesis , Células TH1/inmunología , Células Th2/inmunología , Adolescente , Adulto , Anciano , Animales , Técnicas de Cocultivo , Femenino , Factores de Transcripción Forkhead/genética , Factor de Transcripción GATA3/genética , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Leishmania/inmunología , Leishmaniasis/parasitología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/parasitología , Masculino , Persona de Mediana Edad , Proteínas de Dominio T Box/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Leishmania (Viannia) species are the principal cause of mucosal leishmaniasis. The natural history and pathogenesis of mucosal disease are enigmatic. Parasitological evaluation of mucosal tissues has been constrained by the invasiveness of conventional sampling methods. METHODS: We evaluated the presence of Leishmania in the mucosa of 26 patients with cutaneous leishmaniasis and 2 patients with mucocutaneous leishmaniasis. Swab samples of the nasal mucosa, tonsils, and conjunctiva were analyzed using polymerase chain reaction with LV-B1 primers and Southern blot hybridization. RESULTS: Two patients with mucocutaneous leishmaniasis and 21 (81%) of 26 patients with cutaneous leishmaniasis had Leishmania kinetoplast minicircle DNA (kDNA) in mucosal tissues. kDNA was amplified from swab samples of nasal mucosa from 14 (58%) of 24 patients, tonsils from 13 (46%) of 28 patients, and conjunctiva from 6 (25%) of 24 patients. kDNA was detected in the mucosa of patients with cutaneous disease caused by Leishmania panamensis, Leishmania guyanensis, and Leishmania braziliensis. CONCLUSION: The asymptomatic presence of parasites in mucosal tissues may be common in patients with Leishmania (Viannia) infection.