Alveolar macrophage dysfunction as an early determinant of tuberculosis susceptibility in individuals with type 2 diabetes
Abstract
Type 2 diabetes (T2D) is reshaping the global epidemiology of tuberculosis (TB), yet the biological mechanisms underlying this association remain incompletely defined. Although observational studies consistently show that T2D increases the risk of progression to active TB and worsens clinical outcomes, early immune events within the human lung are challenging to study. In the December 2025 issue of eBio-Medicine, Kleynhans et al. 1 address this gap by analysing bronchoalveolar lavage (BAL) and blood samples from individuals with and without T2D who were exposed to TB, providing new insights into human alveolar macrophages (HAMs), the initial host cells encountered upon inhalation of Mycobacterium tuberculosis.
The study shows that HAMs from individuals with T2D support increased M. tuberculosis growth, despite similar early bacillary uptake compared with HAMs from individuals without T2D. These macrophages display a delayed transcriptional response to infection, increased TNF production, and altered cytokine profiles, indicating a dysregulated inflammatory response. Additionally, HAM gene signatures and reduced neutrophil frequencies in BAL suggest active suppression of neutrophil migration. 1 Collectively, these defects offer a mechanistic explanation for the study's observation that HAMs from individuals with T2D are less capable of controlling early M. tuberculosis growth, a dysfunction that mirrors the more extensive, inflammatory, and slower-resolving pulmonary disease reported clinically in TB-T2D comorbidity.
A notable strength of this study is its demonstration that these defects are pronounced in the lung. Although monocyte-derived macrophages (MDMs) from the same individuals also exhibited impaired polarisation, the dysfunction was substantially greater in HAMs. 1 This distinction is significant for both basic and clinical research, as it underscores how the alveolar environment, influenced by local metabolic, inflammatory, and surfactant factors, imposes constraints on.
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BibTeX
@article{deyts2026alveolar,
title = {{Alveolar macrophage dysfunction as an early determinant of tuberculosis susceptibility in individuals with type 2 diabetes}},
author = {Clara Deyts and Carmen Serrano and Geanncarlo Lugo-Villarino},
journal = {EBioMedicine},
year = {2026},
month = sep,
doi = {10.1016/j.ebiom.2025.106077},
url = {https://hal.science/hal-05771176v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Alveolar macrophage dysfunction as an early determinant of tuberculosis susceptibility in individuals with type 2 diabetes
AU - Clara Deyts
AU - Carmen Serrano
AU - Geanncarlo Lugo-Villarino
PY - 2026
DA - 2026/09/30
JO - EBioMedicine
DO - 10.1016/j.ebiom.2025.106077
UR - https://hal.science/hal-05771176v1
AB - Type 2 diabetes (T2D) is reshaping the global epidemiology of tuberculosis (TB), yet the biological mechanisms underlying this association remain incompletely defined. Although observational studies consistently show that T2D increases the risk of progression to active TB and worsens clinical outcomes, early immune events within the human lung are challenging to study. In the December 2025 issue of eBio-Medicine, Kleynhans et al. 1 address this gap by analysing bronchoalveolar lavage (BAL) and blood samples from individuals with and without T2D who were exposed to TB, providing new insights into human alveolar macrophages (HAMs), the initial host cells encountered upon inhalation of Mycobacterium tuberculosis. The study shows that HAMs from individuals with T2D support increased M. tuberculosis growth, despite similar early bacillary uptake compared with HAMs from individuals without T2D. These macrophages display a delayed transcriptional response to infection, increased TNF production, and altered cytokine profiles, indicating a dysregulated inflammatory response. Additionally, HAM gene signatures and reduced neutrophil frequencies in BAL suggest active suppression of neutrophil migration. 1 Collectively, these defects offer a mechanistic explanation for the study's observation that HAMs from individuals with T2D are less capable of controlling early M. tuberculosis growth, a dysfunction that mirrors the more extensive, inflammatory, and slower-resolving pulmonary disease reported clinically in TB-T2D comorbidity. A notable strength of this study is its demonstration that these defects are pronounced in the lung. Although monocyte-derived macrophages (MDMs) from the same individuals also exhibited impaired polarisation, the dysfunction was substantially greater in HAMs. 1 This distinction is significant for both basic and clinical research, as it underscores how the alveolar environment, influenced by local metabolic, inflammatory, and surfactant factors, imposes constraints on.
SN - 2352-3964
ER -