Altered Polarization and Impaired Phagocytic Activity of Lung Macrophages in People With Human Immunodeficiency Virus and Chronic Obstructive Pulmonary Disease
Kentaro Akata1,2, Janice M Leung3,4, Kei Yamasaki2
1Division of Infection Control and Prevention, University of Occupational and Environmental Health, Japan, Fukuoka, Japan.
Background:
People with human immunodeficiency virus (PWH) have an increased risk of developing chronic obstructive pulmonary disease (COPD).
Methods:
We phenotyped lung macrophages in 4 subgroups-M1 (CD40+CD163-), M2 (CD40-CD163+), double positives (CD40+CD163+), and double negatives and (CD40-CD163-)-and we determined their phagocytic capacity in PWH with and without COPD.
Results:
People with human immunodeficiency virus with COPD have more double-negative macrophages (84.1%) versus PWH without (54.3%) versus controls (23.9%) (P=.004) and reduced phagocytosis (P=.012). Double-negative macrophages had the worst phagocytic capacity (P<.001).
Conclusions:
People with human immunodeficiency virus with COPD have an abundance of nonpolarized macrophages, which have poor phagocytic capacity and therefore predispose PWH to increased risk of disease progression.
Insights
People with HIV and COPD have more non-functional macrophages, leading to reduced phagocytosis and increased disease risk. This highlights a key mechanism in HIV-associated lung disease progression.
Area of Science:
- Immunology
- Pulmonology
- Infectious Diseases
Background:
- People with human immunodeficiency virus (PWH) face a higher risk of developing chronic obstructive pulmonary disease (COPD).
- Understanding the immune mechanisms underlying COPD in PWH is crucial for managing disease progression.
Purpose of the Study:
- To investigate lung macrophage phenotypes and their phagocytic capacity in PWH with and without COPD.
- To identify specific macrophage subsets associated with COPD development in PWH.
Main Methods:
- Lung macrophages were phenotyped into four subgroups: M1, M2, double positives, and double negatives (CD40 and CD163 expression).
- Phagocytic capacity of these macrophage subsets was assessed in PWH with COPD, PWH without COPD, and healthy controls.
Main Results:
- PWH with COPD exhibited a significantly higher proportion of double-negative macrophages (84.1%) compared to PWH without COPD (54.3%) and controls (23.9%).
- Double-negative macrophages demonstrated the poorest phagocytic capacity.
- Reduced overall phagocytosis was observed in PWH with COPD.
Conclusions:
- An abundance of nonpolarized (double-negative) macrophages characterizes PWH with COPD.
- These macrophages possess impaired phagocytic function, contributing to increased susceptibility to lung disease progression in PWH.
- Targeting these non-functional macrophages may offer a therapeutic strategy for COPD in PWH.
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