Altered Polarization and Impaired Phagocytic Activity of Lung Macrophages in People With Human Immunodeficiency Virus

Kentaro Akata1,2, Janice M Leung3,4, Kei Yamasaki2

  • 1Division of Infection Control and Prevention, University of Occupational and Environmental Health, Japan, Fukuoka, Japan.

Abstract

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.