Mtb/HIV co-infection immune microenvironment subpopulations heterogeneity

Background 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. Methods 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. Results 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. Conclusion 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.