Characterization of Distinct Monocyte Subtypes and Immune Features Associated with HIV, Tuberculosis, and Coronary Artery Disease in a Ugandan Cohort Using Mass Cytometry.
| Title: | Characterization of Distinct Monocyte Subtypes and Immune Features Associated with HIV, Tuberculosis, and Coronary Artery Disease in a Ugandan Cohort Using Mass Cytometry. |
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| Authors: | Cobeña-Reyes J; Division of Biomedical Informatics, Cincinnati; Children's Hospital Medical Center, Cincinnati, Ohio.; Wanjalla CN; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee.; The Center for AIDS Health Disparities Research, Nashville, Tennessee.; Veteran's Health Administration, Tennessee Valley Healthcare System, Nashville, Tennessee.; Feria MG; Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio.; Simmons J; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee.; Temu T; Department of Pathology, Mass General Brigham, Harvard Medical School, Boston, Massachusetts.; Nochowicz C; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee.; Arafat SY; Division of Biomedical Informatics, Cincinnati; Children's Hospital Medical Center, Cincinnati, Ohio.; Department of Biostatistics, Health Informatics, and Data Sciences, College of Medicine, University of Cincinnati, Cincinnati, Ohio.; Kityo C; Joint Clinical Research Center, Kampala, Uganda.; Erem G; Makerere University, Kampala, Uganda.; Longenecker CT; Division of Cardiology, Department of Global Health, University of Washington, Seattle, Washington.; Andorf S; Division of Biomedical Informatics, Cincinnati; Children's Hospital Medical Center, Cincinnati, Ohio.; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.; Huaman MA; Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio. |
| Source: | Pathogens & immunity [Pathog Immun] 2026 Jan 29; Vol. 11 (1), pp. 14-38. Date of Electronic Publication: 2026 Jan 29 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Case Western Reserve University Country of Publication: United States NLM ID: 101683909 Publication Model: eCollection Cited Medium: Internet ISSN: 2469-2964 (Electronic) Linking ISSN: 24692964 NLM ISO Abbreviation: Pathog Immun Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Cleveland, OH : Case Western Reserve University, [2016]- |
| Abstract: | Background: Coronary artery disease (CAD), tuberculosis (TB), and HIV are major global health concerns. Individuals affected by one or more of these conditions often exhibit chronic inflammation and immune dysregulation, with monocytes playing a central role. Monocyte subsets are known to expand in individuals with HIV, TB, or CAD, but the mechanisms by which these cells contribute to inflammation and immune responses remain poorly understood.; Methods: We employed high-dimensional mass cytometry to characterize monocyte heterogeneity in 61 Ugandan adults with varying combinations of HIV, TB, and subclinical or overt CAD. An integrative approach was used, combining manual gating, unsupervised clustering, and machine learning to identify distinct monocyte phenotypes associated with CAD and TB. Monocyte activation markers soluble CD14 (sCD14) and sCD163 were measured in plasma. CAD was diagnosed by coronary computed tomography angiography. TB was determined by a questionnaire and interferon-gamma release assay (IGRA) testing.; Results: Participants' demographics and clinical characteristics were similar by CAD or HIV/TB status. Median age was 61 years; 37.7% were female. People living with HIV and latent TB or prior active TB had higher sCD14 plasma levels compared with HIV/TB-negative individuals. Individuals with CAD showed reduced surface expression of the scavenger receptor CD163 on non-classical monocytes. Unsupervised clustering further revealed 2 distinct non-classical monocyte subsets associated with disease states: A CD86dim CX3CR1dim CD45RA+ GPR56+ CXCR3+ subset significantly depleted in individuals with CAD, and a CD86+ CX3CR1++ CD45RA++ GPR56- CD38- CXCR3- subset enriched in individuals with latent TB.; Conclusions: These findings underscore the complexity of the monocyte landscape in CAD progression, particularly in regions where HIV and TB are co-endemic. Our study reveals distinct alterations within 2 non-classical monocyte subpopulations associated with CAD and with HIV/TB, offering mechanistic insights that may support the development of precision biomarkers and immune-targeted therapies across these disease contexts.; (© Pathogens and Immunity 2026.) |
| Competing Interests: | The authors report no relevant conflicts of interest related to this article. |
| Comments: | Update of: bioRxiv. 2025 Aug 27:2025.08.25.672210. doi: 10.1101/2025.08.25.672210.. (PMID: 40909531) |
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| Grant Information: | K23 HL123341 United States HL NHLBI NIH HHS; K01 HL147723 United States HL NHLBI NIH HHS; R01 HL156779 United States HL NHLBI NIH HHS; P30 AR070549 United States AR NIAMS NIH HHS; K23 HL156759 United States HL NHLBI NIH HHS; R03 TR004097 United States TR NCATS NIH HHS |
| Contributed Indexing: | Keywords: Biomarker; CD163; CX3CR1; Coronary Artery Disease; Elastic Net; HIV; Immune Dysregulation; Mass Cytometry; Monocytes; Tuberculosis; Unsupervised Clustering |
| Entry Date(s): | Date Created: 20260205 Date Completed: 20260205 Latest Revision: 20260211 |
| Update Code: | 20260211 |
| PubMed Central ID: | PMC12867109 |
| DOI: | 10.20411/pai.v11i1.945 |
| PMID: | 41640845 |
| Database: | MEDLINE |
Journal Article