Guasconi Lorena, Beccacece Ignacio, Volpini Ximena, Burstein Verónica L, Mena Cristian J, Silvane Leonardo, Almeida Mariel A, Musri Melina Mara, Cervi Laura, Chiapello Laura S
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina.
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba X5000HUA, Argentina.
J Fungi (Basel). 2022 Jul 28;8(8):792. doi: 10.3390/jof8080792.
Lung dendritic cells (DC) are powerful antigen-presenting cells constituted by various subpopulations that differ in terms of their function and origin and differentially regulate cell-mediated antifungal immunity. The lung is the primary target organ of and infections, which makes it essential in the establishment of the first line of anti-cryptococcal defense. However, the lung-specific dynamics and function of DC subsets are poorly understood in cryptococcosis. In this study, we provide evidence for the in vivo function of a conventional langerin-expressing DC1 dendritic cell (LangDC1) population during the first week of intratracheal infection in mice. By using conditional depletion of LangDC1 after diphtheria toxin treatment of LangDTREGFP mice, we demonstrate that these animals better control the fungal infection and produce type 1 and 17 cytokines in the context of a type 2 immune response, favoring a predominance of iNOS over arginase-1 expression by pulmonary cells. Our results suggest that LangDC1 cells play a role in impairing immune response for the clearance of in the early stage of pulmonary infection.
肺树突状细胞(DC)是由各种亚群构成的强大抗原呈递细胞,这些亚群在功能和起源方面存在差异,并对细胞介导的抗真菌免疫进行不同程度的调节。肺是新型隐球菌和荚膜组织胞浆菌感染的主要靶器官,这使其在建立抗隐球菌防御的第一道防线中至关重要。然而,在隐球菌病中,DC亚群的肺特异性动态变化和功能尚不清楚。在本研究中,我们提供了证据,证明在小鼠气管内新型隐球菌感染的第一周,表达传统朗格汉斯蛋白的DC1树突状细胞(LangDC1)群体在体内发挥功能。通过对白喉毒素处理的LangDTREGFP小鼠进行LangDC1的条件性清除,我们证明这些动物能更好地控制真菌感染,并在2型免疫反应的背景下产生1型和17型细胞因子,有利于肺细胞中诱导型一氧化氮合酶(iNOS)的表达超过精氨酸酶-1。我们的结果表明,LangDC1细胞在肺部感染早期对新型隐球菌清除的免疫反应受损中发挥作用。