Rodríguez-Echeverri Carolina, Gómez Beatriz L, González Ángel
Basic and Applied Microbiology Group (MICROBA), School of Microbiology, Universidad de Antioquia, Medellín, Colombia.
Translational Microbiology and Emerging Diseases Research Group (MICROS), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
Mycoses. 2023 Feb;66(2):157-167. doi: 10.1111/myc.13537. Epub 2022 Oct 18.
Mesenchymal stromal cells (MSC) have been widely used not only for tissue regeneration but also for the treatment of various diseases; however, it has been shown that infection of MSCs by different pathogens can attenuate their intrinsic immunomodulatory properties, affecting the proliferation and differentiation of these cells. Currently, the mechanisms by which MSCs respond to pathogen invasion are poorly understood. Therefore, the objective of the present study was to determine if the infection of bone marrow-derived MSCs, with yeasts of the pathogenic fungus Histoplasma capsulatum affects the activation, differentiation and/or proliferation of the MSCs. The results indicate that MSCs have the ability to phagocytose H. capsulatum yeasts but do not exert a notable antifungal effect. On the contrary, the infection of the MSCs with this fungal pathogen not only modulates the expression of inflammatory mediators by a mechanism dependent on TLR2, TLR4 and Dectin-1 but also affects the viability and differentiation capacity of the MSCs. These findings suggest that infection of MSCs by H. capsulatum could not only affect haematopoiesis but also modulate the immune response in the infected host and, furthermore, these MSCs could provide a niche for the fungus, allowing it to persist and evade the immune response of the host.
间充质基质细胞（MSC）不仅已被广泛用于组织再生，还用于治疗各种疾病；然而，研究表明，不同病原体感染MSC可减弱其内在的免疫调节特性，影响这些细胞的增殖和分化。目前，人们对MSC应对病原体入侵的机制了解甚少。因此，本研究的目的是确定骨髓来源的MSC被致病性真菌荚膜组织胞浆菌的酵母感染是否会影响MSC的激活、分化和/或增殖。结果表明，MSC具有吞噬荚膜组织胞浆菌酵母的能力，但未发挥显著的抗真菌作用。相反，这种真菌病原体感染MSC不仅通过依赖TLR2、TLR4和Dectin-1的机制调节炎症介质的表达，还影响MSC的活力和分化能力。这些发现表明，荚膜组织胞浆菌感染MSC不仅可能影响造血，还可能调节受感染宿主的免疫反应，此外，这些MSC可能为真菌提供一个生态位，使其得以持续存在并逃避宿主的免疫反应。
