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This research investigates how chronic alcohol exposure affects alveolar macrophages' response to Mycobacterium tuberculosis infection.

May 20, 2026

C106-11 Chronic Alcohol Exposure and Mycobacterium Tuberculosis Infection Induce Redox Imbalance and Impair Mitochondrial Bioenergetics in Alveolar Macrophages

Key Points

This research investigates how chronic alcohol exposure affects alveolar macrophages' response to Mycobacterium tuberculosis infection.
Used murine alveolar macrophage cell line MH-S and primary human AMs, treated with ethanol and infected with Mtb.
Measured Nox2 and Nox4 levels, reactive species, mitochondrial parameters via qRT-PCR, fluorescence probes, and bioanalyzer.
Assessed release of inflammatory mediators using ELISA.
Mtb significantly increases expression of Nox2 and Nox4, and enhances reactive oxygen species while reducing mitochondrial respiration.
Chronic EtOH further exacerbates these effects, leading to diminished release of pro-inflammatory cytokines like IL-6 and TNF-α.
Observed mitochondrial bioenergetics suppression correlated with redox imbalance in alveolar macrophages.

Abstract

Abstract Rationale Alcohol misuse is linked to increased risk for tuberculosis (TB), but the mechanisms involved are understudied. Alveolar macrophages (AMs) are the first immune cells to encounter inhaled Mycobacterium tuberculosis (Mtb). In prior studies, AMs from alcohol-fed rats were unable to recognize and engulf Mtb. Alcohol also impaired AM immunity via NADPH oxidase (NOX)-mediated excessive oxidative stress and suppressed mitochondrial bioenergetics. We hypothesized that Mtb exposure, both alone and when coupled with EtOH, increase AM Nox2 and Nox4, driving excessive cellular and mitochondrial oxidative stress and mitochondrial dysfunction, impairing AM innate immune response to Mtb. Methods A murine AM cell line, MH-S cells, were treated ± 0.08% EtOH for 3d ± infection with heat-killed Mtb (H37Ra) at a multiplicity of infection (MOI) of 2:1 for the last 4h. De-identified primary human AMs from participants without major comorbidities were treated ± 0.08% EtOH for 3d ± infection with mc26206 (an Mtb auxotroph) at a MOI of 2:1 for the last 4h. Nox2 and Nox4 mRNA and protein levels were measured by qRT-PCR and cytoimmunostaining, respectively. AM reactive species was determined by DCFH-DA analysis, and AM mitochondrial superoxide and hydrogen peroxide were measured by fluorescence molecular probes. Mitochondrial bioenergetics were assessed by Cell Mito Stress Test using an extracellular flux bioanalyzer. AM release of inflammatory mediators was determined by ELISAs. Results Mtb increases AM Nox2 and Nox4 expression, cellular reactive species, mitochondrial superoxide, and hydrogen peroxide; and suppresses mitochondrial basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. Chronic EtOH exacerbates the detrimental effects of Mtb on AMs and impaired AM release of pro-inflammatory mediators (interleukin-6 and tumor necrosis factor α) in response to Mtb. Conclusions AUD may increase susceptibility to TB via exacerbation of AM redox imbalance, mitochondrial bioenergetics suppression, and decreased elucidation of inflammatory cytokines. This abstract is funded by: R01AA026086 (SMY), K23AI134182 (SCA), P01AA029541 (BSS)

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