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Priming with FLO8-deficient Candida albicans induces Th1-biased protective immunity against lethal polymicrobial sepsis

引用

Cellular & Molecular Immunology 2021年第8期18卷 2010-2023页

作者： Quan-Zhen Lv De-Dong Li Hua Han Yi-Heng Yang Jie-Lin Duan Hui-Hui Ma Yao Yu Jiang-Ye Chen Yuan-Ying Jiang Xin-Ming Jia Clinical Medicine Scientific and Technical Innovation Center Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai200092China School of Pharmacy Second Military Medical UniversityShanghai200433China State Key Laboratory of Molecular Biology Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai200031China

The morphological switch between yeast and hyphae of Candida albicans is essential for its interaction with the host defense ***,the lack of understanding of host-pathogen interactions during *** infection greatly hampers the development of effective ***,we found that priming with the *** FLO8-deficient(flo8)mutant,locked in yeast form,protected mice from subsequent lethal *** *** of Dectin-2,a fungus-derivedα-mannan recognition receptor,completely blocked flo8 mutant-induced ***,the flo8 mutant-induced Dectin-2/CARD9-mediated IL-10 production in DCs and macrophages to block thymus atrophy by inhibiting the ***-induced apoptosis of thymic T cells,which facilitated the continuous output of naive T cells from the thymus to the *** recruitment of naive T cells to the spleen enhanced Th1-biased antifungal immune ***,depletion of CD4^(+)T cells or blockade of IL-10 receptor function using specific antibodies in mice completely blocked the protective effects of flo8 mutant priming against *** ***,mannans exposed on the surface of the flo8 mutant were responsible for eliciting protective immunity by inhibiting the ***-induced apoptosis of thymic T cells to sustain the number of naive T cells in the ***,priming with the flo8 mutant extensively protected mice from polymicrobial infection caused by cecal ligation and puncture(CLP)by enhancing Th1-biased immune ***,our findings imply that targeting FLO8 in *** elicits protective immune responses against polymicrobial infections and that mannans extracted from the flo8 mutant are potential immunotherapeutic candidate(s)for controlling infectious diseases.

关键词： fungi infection Candida albicans Protective immunity Thymus atrophy Apoptosis

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