Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4(+) or CD8(+) T Cells for Complete Host Protection.
Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4(+) or CD8(+) T Cells for Complete Host Protection.
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DOI：
10.3389/fcimb.2021.739027
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发表时间：
2021
影响因子：
5.7
通讯作者：
Del Poeta M
中科院分区：
文献类型：
--
作者：
Normile TG;Rella A;Del Poeta M
新型隐球菌是一种真菌病原体，在易感个体中引起危及生命的脑膜脑炎。真菌疫苗的开发一直受到隐球菌病发生在免疫缺陷的事实。我们以前报道过，一个C。新型球菌突变体（Δsgl1）积累的甾醇葡糖苷（SG）是无毒的，即使在CD4+ T细胞耗竭（一种通常与隐球菌病相关的免疫缺陷状况）下，也能对WT攻击提供完全保护。我们发现用Δsgl1免疫后肺中的高水平SG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，与白细胞大量募集到肺部相一致。B或CD8+ T细胞的消耗不影响Δsgl1清除或对WT攻击的保护。尽管CD4+ T细胞耗竭影响清除，但小鼠仍受到保护，表明突变体的清除对于宿主保护不是必需的。只有当CD4+和CD8+ T细胞都被耗尽时，保护作用才丧失，这突出了真菌来源的SG作为免疫佐剂用于保护宿主免受隐球菌感染的先前未探索的作用。
Cryptococcus neoformans 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 C. neoformans mutant (Δsgl1) 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 Δsgl1 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 Δsgl1 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.
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影响因子：
4
作者：
Grebenciucova, Elena;Reder, Anthony T.;Bernard, Jacqueline T.
通讯作者：
Bernard, Jacqueline T.
影响因子：
15.9
作者：
Nanjappa, Som G.;Heninger, Erika;Klein, Bruce
通讯作者：
Klein, Bruce
影响因子：
15.9
作者：
Bryan, Arielle M.;You, Jeehyun Karen;Del Poeta, Maurizio
通讯作者：
Del Poeta, Maurizio
影响因子：
8.8
作者：
Munshi MA;Gardin JM;Singh A;Luberto C;Rieger R;Bouklas T;Fries BC;Del Poeta M
通讯作者：
Del Poeta M
DOI：
10.3390/jof6030142
发表时间：
2020-08-20
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
McEvoy K;Normile TG;Del Poeta M
通讯作者：
Del Poeta M