RESUMO
BACKGROUND: Dendritic cells (DCs) with both proinflammatory and tolerogenic properties have been implicated in modulation of CD4+ T cell responses in many fungal diseases. However, the role of DC in the context of Talaromyces marneffei (T. marneffei) infection has not been determined. In this study, we aimed to study the effect of the yeast form of T. marneffei yeasts on DCs, as well as the role of DCs in modulating T helper 17 (Th17) and regulatory T (Treg) cell responses to the pathogen. METHODS: Mouse bone marrow-derived DCs were stimulated with T. marneffei yeasts for 24 h. Frequencies of CD80 and CD86 expression on DCs and the levels of IL-6, IL-10 and TGF-ß in the culture supernatant of yeast-stimulated DCs were detected by flow cytometry and ELISA, respectively. In co-culture experiments, CD4+ T lymphocytes of mice were isolated from the spleen using magnetic beads and co-cultured with T. marneffei yeasts, with or without DCs for 24 h. The proportions of Th17 and Treg cells in co-culture were detected by flow cytometry. The mRNA levels of RORγt and Foxp3 were detected by RT-PCR. Levels of IL-10 and TGF-ß in the co-culture supernatant were detected by ELISA. RESULTS: The expressions of CD80 and CD86 on DCs were increased, as well as IL-6, IL-10 and TGF-ß levels in the culture supernatant of T. marneffei-stimulated DCs were higher than those in DCs cultured without T. marneffei. In co-culture experiments, in the presence of DCs, T. marneffei promoted Treg expansion and Foxp3 up-regulation but limited Th17 and downregulated RORγt. Levels of IL-10 and TGF-ß were higher in the co-culture containing DCs than without DCs. CONCLUSION: Our findings demonstrated that the interaction between DCs and T. marneffei could promote Treg expansion but not Th17 generation. These findings provide a mechanism by which DCs may promote immune tolerance in T. marneffei infection.
RESUMO
Some subtropical regions with similar climatic conditions to melioidosis-endemic areas, such as southern Guangxi, may be new endemic zones for melioidosis. We retrospectively reviewed seven culture-proven melioidosis patients from October 2006 to March 2015. Their clinical characteristics, diagnosis, and treatment, and the geographical and environmental factors were analyzed. Seven male patients lived at latitudes of 21-23°N in Beihai, Nanning, Chongzuo City of the Guangxi Province. Symptom onset occurred during the rainy season. All patients had pneumonia, six patients had diabetes, five patients had a history of wounds or exposure to soil or water, and two patients had liver and spleen abscesses. Most patients were misdiagnosed before the confirmatory laboratory testing. The final diagnosis was confirmed as melioidosis by isolation of Burkholderia pseudomallei in a culture of blood or pus. The 6- to 17-month treatment included carbapenems, ceftazidime, or other antibiotics active against the organism in vitro. All patients initially appeared cured, but two subsequently had recurrent melioidosis. In non-highly endemic areas, there is often a lack of awareness of melioidosis, and this leads to misdiagnoses. Other subtropical regions with climatic conditions similar to the highly melioidosis-endemic areas such as southern Guangxi may also be melioidosis endemic.
