Shu Fangyi, Thammasit Patcharin, Pruksaphon Kritsada, Nosanchuk Joshua D, Youngchim Sirida
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Anatomy, Youjiang Medical University for Nationalities, Baise 533000, China.
Pathogens. 2022 Dec 2;11(12):1465. doi: 10.3390/pathogens11121465.
Talaromyces marneffei, a dimorphic fungus, exhibits temperature-dependent growth, existing in a filamentous form at 25 °C and as a yeast at 37 °C. Several studies have highlighted the important roles of macrophages in defense against T. marneffei infection. However, the immune responses to the interaction of macrophages with T. marneffei cells during phase transition require further investigation. This study reports the expression of cytokine profiles in human THP-1 cells during infection by T. marneffei. THP-1 cells were infected with T. marneffei conidia at different multiplicity of infections (MOIs). Surviving conidia transformed into yeasts after phagocytosis by macrophages, and the number of yeasts gradually increased over 36 h. The transcription and secretion levels of pro- and anti-inflammatory cytokines were examined at different times by qRT-PCR and ELISA. Transcription levels of IL-8, IL-12, IL-1β, and TNF-α increased significantly at 12 or 24 h and then slightly decreased at 36 h. In contrast, the transcription levels of IL-6, IL-10, and TGF-β gradually increased at all MOIs. The levels of IL-6 and IL-10 secretion corresponded to their levels of transcription. These results indicated that as the number of intracellular yeasts increased, the infected macrophages first underwent slight M1 polarization before shifting to M2 polarization. This polarization transition was confirmed by the fungicidal ability and the expression of macrophage surface markers. By inducing the M2-type polarization of macrophages, the intracellular T. marneffei cells can successfully evade the immune response. Our study provides a novel insight into the immune characterization during the transition of T. marneffei infection and could further contribute to possible diagnostic and therapeutic interventions for this infection.
马尔尼菲篮状菌是一种双相真菌,具有温度依赖性生长特性,在25℃时呈丝状形态,在37℃时为酵母形态。多项研究强调了巨噬细胞在抵御马尔尼菲篮状菌感染中的重要作用。然而,巨噬细胞与马尔尼菲篮状菌细胞在相变过程中相互作用的免疫反应仍需进一步研究。本研究报告了马尔尼菲篮状菌感染期间人THP-1细胞中细胞因子谱的表达情况。THP-1细胞以不同的感染复数(MOI)感染马尔尼菲篮状菌分生孢子。存活的分生孢子在被巨噬细胞吞噬后转变为酵母,酵母数量在36小时内逐渐增加。通过qRT-PCR和ELISA在不同时间检测促炎和抗炎细胞因子的转录和分泌水平。IL-8、IL-12、IL-1β和TNF-α的转录水平在12或24小时显著升高,然后在36小时略有下降。相反,IL-6、IL-10和TGF-β的转录水平在所有MOI下均逐渐升高。IL-6和IL-10的分泌水平与其转录水平相对应。这些结果表明,随着细胞内酵母数量的增加,被感染的巨噬细胞首先经历轻微的M1极化,然后转变为M2极化。这种极化转变通过杀菌能力和巨噬细胞表面标志物的表达得到证实。通过诱导巨噬细胞的M2型极化,细胞内的马尔尼菲篮状菌细胞能够成功逃避免疫反应。我们的研究为马尔尼菲篮状菌感染转变过程中的免疫特征提供了新的见解,并可能进一步有助于针对这种感染的诊断和治疗干预。