Campuzano Althea, Castro-Lopez Natalia, Wozniak Karen L, Leopold Wager Chrissy M, Wormley Floyd L
Department of Biology, The University of Texas at San Antonio, San Antonio, TX, United States of America.
South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United States of America.
PLoS One. 2017 Jan 20;12(1):e0169347. doi: 10.1371/journal.pone.0169347. eCollection 2017.
C-type lectin receptors (CLRs) are diverse, trans-membrane proteins that function as pattern recognition receptors (PRRs) which are necessary for orchestrating immune responses against pathogens. CLRs have been shown to play a major role in recognition and protection against fungal pathogens. Dectin-3 (also known as MCL, Clecsf8, or Clec4d) is a myeloid cell-specific CLR that recognizes mycobacterial trehalose 6,6'-dimycolate (TDM) as well as α-mannans present in the cell wall of fungal pathogens. To date, a potential role for Dectin-3 in the mediation of protective immune responses against C. neoformans has yet to be determined. Consequently, we evaluated the impact of Dectin-3 deficiency on the development of protective immune responses against C. neoformans using an experimental murine model of pulmonary cryptococcosis. Dectin-3 deficiency did not lead to increased susceptibility of mice to experimental pulmonary C. neoformans infection. Also, no significant differences in pulmonary leukocyte recruitment and cytokine production were observed in Dectin-3 deficient mice compared to wild type infected mice. In addition, we observed no differences in uptake and anti-cryptococcal activity of Dectin-3 deficient dendritic cells and macrophages. Altogether, our studies show that Dectin-3 is dispensable for mediating protective immune responses against pulmonary C. neoformans infection.
C型凝集素受体（CLRs）是多种多样的跨膜蛋白，作为模式识别受体（PRRs）发挥作用，而模式识别受体是协调针对病原体的免疫反应所必需的。已证明CLRs在识别和抵御真菌病原体方面发挥主要作用。树突状细胞特异性C型凝集素-3（也称为MCL、Clecsf8或Clec4d）可识别分枝杆菌海藻糖6,6'-二霉菌酸酯（TDM）以及真菌病原体细胞壁中存在的α-甘露聚糖。迄今为止，树突状细胞特异性C型凝集素-3在介导针对新型隐球菌的保护性免疫反应中的潜在作用尚未确定。因此，我们使用实验性小鼠肺隐球菌病模型评估了树突状细胞特异性C型凝集素-3缺陷对针对新型隐球菌的保护性免疫反应发展的影响。树突状细胞特异性C型凝集素-3缺陷并未导致小鼠对实验性肺新型隐球菌感染的易感性增加。此外，与野生型感染小鼠相比，在树突状细胞特异性C型凝集素-3缺陷小鼠中未观察到肺白细胞募集和细胞因子产生的显著差异。此外，我们在树突状细胞特异性C型凝集素-3缺陷的树突状细胞和巨噬细胞的摄取和抗隐球菌活性方面未观察到差异。总之，我们的研究表明，树突状细胞特异性C型凝集素-3对于介导针对肺新型隐球菌感染的保护性免疫反应是可有可无的。
