2026-08-06 バージニア工科大学（Virginia Tech）
＜関連情報＞
- https://news.vt.edu/articles/2026/08/vetmed-research-cryptococcus.html
- https://journals.asm.org/doi/10.1128/mbio.01528-26
潜在性クリプトコッカス症における逆説的なTh1活性化とCTLA-4調節は有益である Paradoxical Th1 activation and CTLA-4 regulation is beneficial during latent cryptococcosis
M. Ding, J. Drnevich, J. M. Yoder, E. V. Dang, K. Nielsen
mBio Published:22 July 2026
DOI:https://doi.org/10.1128/mbio.01528-26
ABSTRACT
Cryptococcus neoformans is the predominant causative agent of cryptococcal meningitis in immunocompromised individuals. Conversely, in immunocompetent individuals, C. neoformans establishes a latent pulmonary infection characterized by a paucity of clinical symptoms. Using a mouse inhalation model of latent C. neoformans infection, we previously showed that CD4 T cells are necessary for preventing fungal proliferation in the lungs. In the current study, we performed single-cell RNA sequencing (scRNA-seq) and found that the CD4 T-cell response was both highly heterogeneous and dichotomous during pulmonary C. neoformans infection, with concomitant expression of genes related to Th1 polarization (Tbx21 and Ifng) and immune regulation (Ctla4). First, we demonstrated that cells with Th1-like phenotypes are necessary and sufficient to control latent infection via adoptive transfer of Tbet-positive cells into infection-matched CD4-depleted recipient mice. Second, scRNA-seq analysis revealed that the subpopulation of effector CD4 T cells that co-expressed Ctla4 and Gata3 was significantly higher than a subpopulation that co-expressed Ctla4 and Tbx21. Furthermore, our data suggested that CTLA-4 upregulation is beneficial against C. neoformans infection as CTLA-4 blockade promoted fungal proliferation. Thus, we propose a model wherein Th1 control of latent C. neoformans infection is supported by CTLA-4 suppression of detrimental Th2 activation.
