Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, United States.
Division of Infectious Diseases, School of Medicine, Stony Brook University, Stony Brook, NY, United States.
Front Cell Infect Microbiol. 2021 Sep 8;11:739027. doi: 10.3389/fcimb.2021.739027. eCollection 2021.
is a fungal pathogen causing life-threatening meningoencephalitis in susceptible individuals. Fungal vaccine development has been hampered by the fact that cryptococcosis occurs during immunodeficiency. We previously reported that a mutant (Δ) accumulating sterylglucosides (SGs) is avirulent and provides complete protection to WT challenge, even under CD4 T cell depletion, an immunodeficient condition commonly associated with cryptococcosis. We found high levels of SGs in the lungs post-immunization with Δ that decreased upon fungal clearance. Th1 cytokines increased whereas Th2 cytokines concurrently decreased, coinciding with a large recruitment of leukocytes to the lungs. Depletion of B or CD8 T cells did not affect either Δ clearance or protection from WT challenge. Although CD4 T cell depletion affected clearance, mice were still protected indicating that clearance of the mutant was not necessary for host protection. Protection was lost only when both CD4 and CD8 T cells were depleted, highlighting a previously unexplored role of fungal-derived SGs as an immunoadjuvant for host protection against cryptococcosis.
荚膜组织胞浆菌是一种真菌病原体，可导致易感个体发生危及生命的脑膜脑炎。由于隐球菌病发生在免疫缺陷时，真菌疫苗的开发一直受到阻碍。我们之前曾报道，积累甾醇葡糖苷（SGs）的 突变体（Δ）是无毒的，可提供对 WT 挑战的完全保护，即使在 CD4 T 细胞耗竭的免疫缺陷条件下也是如此，这种免疫缺陷条件通常与隐球菌病有关。我们发现，用 Δ 免疫后，肺部的 SGs 水平很高，在真菌清除后降低。Th1 细胞因子增加，而 Th2 细胞因子同时减少，同时白细胞大量募集到肺部。B 细胞或 CD8 T 细胞耗竭既不影响 Δ 清除，也不影响对 WT 挑战的保护。尽管 CD4 T 细胞耗竭会影响清除，但小鼠仍受到保护，这表明清除突变体对于宿主保护并不必要。只有当 CD4 和 CD8 T 细胞都被耗尽时，保护才会丧失，这突出了真菌来源的 SGs 作为宿主对抗隐球菌病免疫佐剂的先前未被探索的作用。
