Related Experiment Video
Updated: Feb 6, 2026
Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Characterization of Distinct Monocyte Subtypes and Immune Features Associated with HIV, Tuberculosis, and Coronary
José Cobeña-Reyes1, Celestine N Wanjalla2,3,4, Manuel G Feria5
1Division of Biomedical Informatics, Cincinnati; Children's Hospital Medical Center, Cincinnati, Ohio.
Insights
Coronary artery disease (CAD), tuberculosis (TB), and HIV impact monocytes. Distinct non-classical monocyte subsets are altered in individuals with CAD and HIV/TB, offering insights for targeted therapies.
Area of Science:
- Immunology
- Cardiovascular Disease
- Infectious Disease
Background:
- Coronary artery disease (CAD), tuberculosis (TB), and HIV are significant global health issues.
- Monocytes play a key role in chronic inflammation and immune dysregulation associated with these diseases.
- Understanding monocyte heterogeneity is crucial for elucidating disease mechanisms.
Purpose of the Study:
- To characterize monocyte heterogeneity in Ugandan adults with co-occurring HIV, TB, and CAD.
- To identify distinct monocyte phenotypes associated with CAD and TB.
- To explore the role of monocyte subsets in inflammation and immune responses.
Main Methods:
- Mass cytometry was used to analyze monocyte heterogeneity in 61 Ugandan adults.
- An integrated approach combining manual gating, unsupervised clustering, and machine learning was employed.
- Plasma levels of soluble CD14 (sCD14) and sCD163 were measured, and CAD/TB status was confirmed.
Main Results:
- Individuals with HIV and TB showed elevated sCD14 plasma levels.
- CAD was associated with reduced CD163 expression on non-classical monocytes.
- Two distinct non-classical monocyte subsets were identified: one depleted in CAD, another enriched in latent TB.
Conclusions:
- Monocyte alterations are complex in CAD, especially in HIV/TB co-endemic regions.
- Distinct non-classical monocyte subpopulations are associated with CAD and HIV/TB.
- Findings may inform the development of precision biomarkers and immune-targeted therapies.
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.
Related Concept Videos
01:30Coronary Artery Disease I: Introduction
01:26Coronary Artery Disease II: Pathophysiology
01:27Coronary Artery Disease V: Interprofessional Care
01:30Coronary Artery Disease III: Clinical Manifestations
01:26Coronary Artery Disease IV: Preventive Measures
01:20Special Features of Adaptive Immunity
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...