1485. Landscape of peripheral blood mononuclear cell single-cell transcriptomes in HIV-infected patients with cryptococcal meningitis

Abstract

Abstract Background Cryptococcal meningitis (CM) is a lethal opportunistic infection in patients with human immunodeficiency virus (HIV); however, the immunopathogenic mechanisms underlying HIV-associated cryptococcal meningitis (HIV-CM) remain largely unknown. Methods Here, using the single-cell nucleus sequencing approach, we compared peripheral blood mononuclear cell (PBMC) transcriptomic alterations among ART-naïve HIV-CM patients (N=8), ART-naïve HIV-infected individuals (N=8), and healthy controls (HC, N=8). Additionally, alteration of the single-cell transcriptomes of HIV-CM patients before and after four-week antifungal treatment was also analyzed, to estimate the influence of treatment. Results In total, we obtained 318,718 PBMCs and identified 20 cell subclusters based on gene expression. In our PBMC sample, we observed the significantly decreased percentage of CD4+ T-cells and NK cells, as well as an increased percentage of CD14 monocytes in HIV-CM patients, relative to HC. Only the percentage of CD4+ T-cells was significantly altered in HIV-CM patients, compared to HIV-infected individuals. Moreover, after four-week of antifungal treatment, the percentage of these three cell types were significantly altered. After treatment, the proportion of CD4+ T-cells in HIV-CM patients was observed to be lower compared to HC, but was comparable to HIV-infected individuals. The relative fractions of NK and CD14 monocytes were also reversed, to revert to normal levels. The functions of the HIV-CM-specific differentially expressed genes (DEGs) among the three cell types are related to cytoplasmic translation, signal recognition particle (SRP)-dependent co-translational protein targeting, viral processes, and others. After antifungal treatment, the rate of reversal of the DEGs ranged from 11.7% to 22.9%. The reversed genes are mainly associated with neutrophil degranulation and immune system processes. Conclusion Together, the preceding findings suggest that the degree of change to the transcriptomes of PBMCs may be utilized as a potential marker for HIV-CM patients and for functional assessment of antifungal treatment. Furthermore, the disturbed molecular pathways may aid in understanding fundamental immunopathogenic pathways inherent to HIV-CM patients. Disclosures All Authors: No reported disclosures