Rodríguez-Echeverri Carolina, Gómez Beatriz L, González Ángel
Basic and Applied Microbiology Group (MICROBA), School of Microbiology, Universidad de Antioquia, Medellín 050010, Colombia.
Translational Microbiology and Emerging Diseases Research Group (MICROS), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia.
J Fungi (Basel). 2022 Oct 20;8(10):1108. doi: 10.3390/jof8101108.
Hematopoietic stem cells (HSCs), a multipotent and self-renewing population responsible for the generation and maintenance of blood cells, have been the subject of numerous investigations due to their therapeutic potential. It has been shown that these cells are able to interact with pathogens through the TLRs that they express on their surface, affecting the hematopoiesis process. However, the interaction between hematopoietic stem and progenitor cells (HSPC) with fungal pathogens such as has not been studied. Therefore, the objective of the present study was to determine if the interaction of HSPCs with yeasts affects the hematopoiesis, activation, or proliferation of these cells. The results indicate that HSPCs are able to adhere to and internalize yeasts through a mechanism dependent on TLR2, TLR4, and Dectin-1; however, this process does not affect the survival of the fungus, and, on the contrary, such interaction induces a significant increase in the expression of IL-1β, IL-6, IL-10, IL-17, TNF-α, and TGF-β, as well as the immune mediators Arg-1 and iNOS. Moreover, induces apoptosis and alters HSPC proliferation. These findings suggest that directly modulates the immune response exerted by HPSC through PRRs, and this interaction could directly affect the process of hematopoiesis, a fact that could explain clinical manifestations such as anemia and pancytopenia in patients with severe histoplasmosis, especially in those with fungal spread to the bone marrow.
造血干细胞（HSCs）是一类多能且能自我更新的细胞群体，负责血细胞的生成和维持，因其治疗潜力而成为众多研究的对象。研究表明，这些细胞能够通过其表面表达的Toll样受体（TLRs）与病原体相互作用，从而影响造血过程。然而，造血干细胞和祖细胞（HSPC）与诸如[此处原文缺失真菌名称]等真菌病原体之间的相互作用尚未得到研究。因此，本研究的目的是确定HSPC与[此处原文缺失真菌名称]酵母的相互作用是否会影响这些细胞的造血、激活或增殖。结果表明，HSPC能够通过一种依赖于TLR2、TLR4和Dectin-1的机制黏附并内化[此处原文缺失真菌名称]酵母；然而，这一过程并不影响真菌的存活，相反，这种相互作用会导致IL-1β、IL-6、IL-10、IL-17、TNF-α和TGF-β以及免疫介质精氨酸酶-1（Arg-1）和诱导型一氧化氮合酶（iNOS）的表达显著增加。此外，[此处原文缺失真菌名称]会诱导细胞凋亡并改变HSPC的增殖。这些发现表明，[此处原文缺失真菌名称]通过模式识别受体（PRRs）直接调节HPSC发挥的免疫反应，并且这种相互作用可能直接影响造血过程，这一事实可以解释重症组织胞浆菌病患者出现贫血和全血细胞减少等临床表现的原因，尤其是那些真菌扩散至骨髓的患者。
