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Updated: Jun 10, 2025
An In Vitro Model for Measuring Immune Responses to Malaria in the Context of HIV Co-infection
Published on: October 6, 2015
Mtb/HIV co-infection immune microenvironment subpopulations heterogeneity
Jiamin Gao1, Xianzhen Huang1, Qingdong Zhu1
1Laboratory 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.
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.
