Laboratory of Infectious Disease, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning) and The Fourth People's Hospital of Nanning, Nanning 530023, China; Department of Tuberculosis, The Fourth People's Hospital of Nanning, Nanning 530023, China.
Laboratory of Infectious Disease, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning) and The Fourth People's Hospital of Nanning, Nanning 530023, China; Department of Tuberculosis, The Fourth People's Hospital of Nanning, Nanning 530023, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113341. doi: 10.1016/j.intimp.2024.113341. Epub 2024 Oct 14.
The co-infection of human immunodeficiency virus type 1 (HIV-1) and tuberculosis poses a lethal threat. Currently, our understanding of the altered immune responses and diverse immune cell subpopulations triggered by dual pathogen infections remains inadequate.
We utilized single-cell RNA sequencing data from the Gene Expression Omnibus database and the China National GeneBank Nucleotide Sequence Archive to study peripheral blood mononuclear cells from individuals infected with HIV-1 and those co-infected with Mycobacterium tuberculosis (Mtb)/HIV. We investigated cellular components, signaling pathways, biological functions, developmental trajectories, and gene regulatory networks among different cells to determine cellular heterogeneity in the progression of Mtb/HIV co-infection.
We constructed a single-cell global transcriptional landscape of Mtb/HIV co-infection, revealing heterogeneity among various cell subpopulations. CD4 T_RACK1_STAT1 subpopulation may participate in the JAK-STAT signaling pathway through RACK1-mediated transcriptional regulation of STAT1, potentially mediating the immune response in patients. Targeting CD8 T_RACK1_TIGIT subpopulation via RACK1 may help restore the effector capacity of CD8 T cells. Additionally, Mono_HSP90AA1 and Mono_APOBEC3A subpopulations were positioned at the endpoints of monocyte differentiation trajectories in different patients, suggesting their significant roles in distinct types of immune responses. CTL_GNLY and NK_HSPA1A subpopulations were specifically enriched in three distinct HIV-infected patient groups, indicating their crucial roles in the immune cytotoxicity associated with Mtb/HIV co-infection.
The immune system disruptions caused by HIV-1 infection are further exacerbated by co-infection with Mtb. This compounded effect leads to significant heterogeneity in immune cell subpopulations among co-infected individuals, promoting immune system dysfunction.
人类免疫缺陷病毒 1 型（HIV-1）和结核病的合并感染构成了致命威胁。目前，我们对于双重病原体感染引发的免疫反应改变和不同免疫细胞亚群的了解还不够充分。
我们利用来自基因表达综合数据库（Gene Expression Omnibus database）和中国国家基因库核苷酸序列档案（China National GeneBank Nucleotide Sequence Archive）的单细胞 RNA 测序数据，研究了感染 HIV-1 的个体和感染结核分枝杆菌（Mycobacterium tuberculosis，Mtb）/HIV 的个体的外周血单核细胞。我们研究了不同细胞之间的细胞成分、信号通路、生物学功能、发育轨迹和基因调控网络，以确定 Mtb/HIV 合并感染进展过程中的细胞异质性。
我们构建了 Mtb/HIV 合并感染的单细胞全转录组景观，揭示了不同细胞亚群之间的异质性。CD4 T_RACK1_STAT1 亚群可能通过 RACK1 介导的 STAT1 转录调控参与 JAK-STAT 信号通路，潜在地介导患者的免疫反应。通过 RACK1 靶向 CD8 T_RACK1_TIGIT 亚群可能有助于恢复 CD8 T 细胞的效应器功能。此外，Mono_HSP90AA1 和 Mono_APOBEC3A 亚群在不同患者的单核细胞分化轨迹的终点处定位，表明它们在不同类型的免疫反应中具有重要作用。CTL_GNLY 和 NK_HSPA1A 亚群在三个不同的 HIV 感染患者群体中特异性富集，表明它们在与 Mtb/HIV 合并感染相关的免疫细胞毒性中起着关键作用。
HIV-1 感染引起的免疫系统破坏因合并感染 Mtb 而进一步加剧。这种复合效应导致合并感染个体的免疫细胞亚群存在显著的异质性，促进了免疫系统功能障碍。
