Immune Impacts of Fire Smoke Exposure

Authors

• Mary M Johnson
• Abhinav Kaushik
• Olivia A Kline
• Eric M Smith
• Xiaoying Zhou
• Yagiz Pat
• Laura Buergi
• Juan Aguilera
• Shifaa Alkotob
• Elisabeth M Simonin
• Alberto Favaro
• Miguel Couto
• Oscar Bennett
• R Sharon Chinthrajah
• Ella Parsons
• Mohamed Shamji
• Marshall Burke
• Melissa Bondy
• Mubeccel Akdis
• Cezmi A Akdis
• Kari C Nadeau

Language

English

Publication Date

9-1-2025

Journal

Nature Medicine

DOI

10.1038/s41591-025-03777-6

PMID

40571754

PMCID

PMC12696577

PubMedCentral® Posted Date

12-12-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Fire smoke exposure has become a global health concern and is associated with increased morbidity and mortality. There is a lack of understanding of the specific immune mechanisms involved in smoke exposure with preventative and targeted interventions needed. After exposure to fire smoke, which includes PM2.5, toxic metals and per- and polyfluoroalkyl substances (PFAS), epidemiology-based studies demonstrate increases in respiratory (e.g. asthma exacerbations), cardiac (e.g. myocardial infarctions, arrhythmias), neurologic (e.g. stroke) and pregnancy-related (e.g. low birthweight, premature births) outcomes. However, mechanistic studies exploring how smoke exposure disrupts cellular homeostasis are lacking. Therefore, we collected blood from smoke-exposed individuals (n=31) and age- and sex-matched non smoke-exposed controls (n=29) and investigated these complex interactions using a single-cell exposomic approach based on both methylation and mass cytometry outcomes. Overall, our data demonstrated a strong association between smoke exposure and methylation at 133 disease-relevant gene loci, and immunophenotyping revealed increased homing and activation biomarkers. We developed an application of mass cytometry to analyze single cell/metal binding and found, for example, increased levels of mercury in dead cells and cadmium in the live and dead cell populations. Moreover, mercury levels were associated with years of smoke exposure. Several epigenetic sites across multiple chromosomes were associated with individual toxic metal isotopes in single immune cells. Our methods for detecting the effect of smoke exposure at the single-cell level and study results may help to determine the timing of exposures and identify specific molecular targets that could be modified to prevent and manage exposure to smoke.

Keywords

Humans, Female, Smoke, Male, Adult, Middle Aged, DNA Methylation, Fires, Case-Control Studies, Environmental Exposure, Biomarkers

Published Open-Access

yes

Recommended Citation

Johnson, Mary M; Kaushik, Abhinav; Kline, Olivia A; et al., "Immune Impacts of Fire Smoke Exposure" (2025). Faculty, Staff and Student Publications. 3525.
https://digitalcommons.library.tmc.edu/uthmed_docs/3525