The Immune Cost of Dirty Air

"About 99% of people breathe air that does not comply with the WHO Air Quality Guidelines." - WHO, 2021

Air pollution is undoubtedly increasing around the world. Every time I see a high AQI reading on my weather app, I wonder just how bad it's going to be for us.

Key Takeaway

High AQI levels are not just a warning for our lungs. It may also be a warning for our immune system. Fine particles like PM_2.5 can reach deep into the lungs, disrupt immune cells, and leave the body more inflamed but less prepared to fight infection.

What chemicals constitute air pollutants?

The primary and most well-studied air pollutants are particulate matter (PM) of varying diameters. They contain complex mixtures of adsorbed substances, such as metals, toxins, microbes, and polycyclic aromatic hydrocarbons. Among them, PM with a diameter less than 2.5 micrometers (PM_2.5) is the most extensively studied, and for good reason.

Why are they bad?

Their small size allows PM_2.5 particles to slip past the upper respiratory tract and settle deep within the smaller airways. From there, immune cells like macrophages and dendritic cells can endocytose them. PM_2.5 activates receptors like Toll-like receptors (TLRs) and Aryl hydrocarbon receptors (AhRs), triggering inflammation and ROS production. This weakens the epithelial barrier, allowing PM_2.5 to leak into the dense pulmonary capillary network underneath. Once particles reach the capillaries, they can be easily pumped to virtually every organ in the body, driving systemic inflammation. (Cui et al. 2025)

Effect of PM_2.5 on immune cells

Macrophages are one of the first immune cells to encounter PM_2.5. Macrophages can easily phagocytose PM_2.5 particles. Moreover, studies show that PM_2.5 activates TLRs, triggering inflammation that recruits other immune cells to the site. (Cui et al. 2025)

In mice exposed to PM_2.5, large numbers of neutrophils flooded the lungs. Single-cell RNA sequencing revealed that these neutrophils had impaired phagocytic function due to increased PD-L1 expression. (Luo et al. 2024) This shift in the neutrophil population left the mice more susceptible to bacterial infections.

Dendritic cells (DCs) didn't fare any better. PM_2.5 exposure disrupted their endolysosomal signaling, largely because DCs were endocytosing non-degradable PM_2.5 particles that they couldn't break down. In cell-based studies, DC functions like phagocytosis, endocytosis, and interferon production were all impaired. (Nakahira et al. 2025) A study of the effects of PM_2.5 inhalation in a juvenile mouse model found that DCs in the lungs exhibited reduced antigen presentation and increased oxidative phosphorylation. (Gui et al. 2025)

Taken together, all this inflammation in the lungs leads to organ damage and leaves the body more vulnerable to bacterial and viral infections.

Adaptive immunity

Since DCs bridge the innate and adaptive immune systems, weakened DC function points to weakened adaptive responses as well. Even macrophages were found to be crucial in determining downstream T-cell responses. For example, In an in-vitro model, macrophages were necessary to facilitate cytokine secretion from CD4+ and CD8+ T cells exposed to PM_2.5. (Ma et al. 2017)

Chronic PM_2.5 exposure in mice led to increased recruitment of CXCR3+ T cells and a pro-inflammatory Th1 response in the lungs. (Deiuliis et al. 2012) PM exposure has also been shown to reduce B-cell numbers while increasing T cells. (Jo et al. 2025) Lymphocytes, including CD4+T cells and NK cells in juvenile mice exposed to PM_2.5, showed altered ribosomal activity and protein synthesis pathways. (Gui et al. 2025)

Why does it matter?

As explained above, PM exposure significantly impacts our ability to resist bacterial and viral infections. Mechanistically, PM_2.5 taken up by macrophages and dendritic cells reduces their immune activity and triggers inflammation. Less effective innate immunity carries over to a weakened adaptive immune system as well. (Marín-Palma et al. 2023)

For example, long-term PM_2.5 exposure has been linked to a higher risk of autoimmune disorders like systemic autoimmune rheumatic diseases (SARDs). (Zhao et al. 2025) A 2022 study reported that particulate matter actually clogged the lymph nodes connected to the lungs, impairing their ability to clear harmful pathogens. (Ural et al. 2022) This effect was worse among the elderly, who are already vulnerable to respiratory viral infections such as COVID-19. Wildfire-derived PM has been shown to cause neuroinflammation and contribute to aging-associated neurodegenerative disorders in mouse models. (Scieszka et al. 2022) 

Understanding how PM affects immune responses helps us develop new treatments to block these effects, especially for transplant patients and other immunocompromised groups. These studies also matter to our brave firefighters who work to contain dangerous wildfires and show higher inflammatory levels after exposure to PM. (Main et al. 2020) Acknowledging the side effects of rising air pollution can help shape public policy.

References

Cui, Cui, Rui Yang, Hao Chen, et al. 2025. “Air Toxins Disorder the NF-kB Pathway Leads to Immune Disorders and Immune Diseases in the Human Health.” Ecotoxicology and Environmental Safety 302 (September): 118474. https://doi.org/10.1016/j.ecoenv.2025.118474.

Deiuliis, Jeffrey A., Thomas Kampfrath, Jixin Zhong, et al. 2012. “Pulmonary T Cell Activation in Response to Chronic Particulate Air Pollution.” American Journal of Physiology - Lung Cellular and Molecular Physiology 302 (4): L399–409. https://doi.org/10.1152/ajplung.00261.2011.

Gui, Biyu, Yu Li, Kuan Li, et al. 2025. “PM2.5 Induces Cell-Specific Transcriptomic Alterations in the Lungs of Juvenile Mice.” Journal of Inflammation Research 18 (July): 9951–66. https://doi.org/10.2147/JIR.S514437.

Jo, Yuna, Bo-Young Kim, So Min Lee, et al. 2025. “Particulate Matter Exposure Induces Pulmonary TH2 Responses and Oxidative Stress-Mediated NRF2 Activation in Mice.” Redox Biology 82 (May): 103632. https://doi.org/10.1016/j.redox.2025.103632.

Luo, Li, Manling Jiang, Ying Xiong, et al. 2024. “Fine Particulate Matter 2.5 Induces Susceptibility to Pseudomonas Aeruginosa Infection via Expansion of PD-L1high Neutrophils in Mice.” Respiratory Research 25 (1): 90. https://doi.org/10.1186/s12931-023-02640-x.

Ma, Qin-Yun, Da-Yu Huang, Hui-Jun Zhang, Shaohua Wang, and Xiao-Feng Chen. 2017. “Exposure to Particulate Matter 2.5 (PM2.5) Induced Macrophage-Dependent Inflammation, Characterized by Increased Th1/Th17 Cytokine Secretion and Cytotoxicity.” International Immunopharmacology 50 (September): 139–45. https://doi.org/10.1016/j.intimp.2017.06.019.

Main, Luana C., Alexander P. Wolkow, Jamie L. Tait, et al. 2020. “Firefighter’s Acute Inflammatory Response to Wildfire Suppression.” Journal of Occupational and Environmental Medicine 62 (2): 145–48. https://doi.org/10.1097/JOM.0000000000001775.

Marín-Palma, Damariz, Geysson Javier Fernandez, Julian Ruiz-Saenz, Natalia A. Taborda, Maria T. Rugeles, and Juan C. Hernandez. 2023. “Particulate Matter Impairs Immune System Function by Up-Regulating Inflammatory Pathways and Decreasing Pathogen Response Gene Expression.” Scientific Reports 13 (1): 12773. https://doi.org/10.1038/s41598-023-39921-w.

Nakahira, Yuki, Daisuke Otomo, Tomoaki Okuda, and Akira Onodera. 2025. “Sub-Toxic Exposure to DEPs and PM2.5 Impairs Dendritic Cell Function Through Intracellular Particle Accumulation.” Journal of Xenobiotics 15 (5): 142. https://doi.org/10.3390/jox15050142.

Scieszka, David, Russell Hunter, Jessica Begay, et al. 2022. “Neuroinflammatory and Neurometabolomic Consequences From Inhaled Wildfire Smoke-Derived Particulate Matter in the Western United States.” Toxicological Sciences 186 (1): 149–62. https://doi.org/10.1093/toxsci/kfab147.

Ural, Basak B., Daniel P. Caron, Pranay Dogra, et al. 2022. “Inhaled Particulate Accumulation with Age Impairs Immune Function and Architecture in Human Lung Lymph Nodes.” Nature Medicine 28 (12): 2622–32. https://doi.org/10.1038/s41591-022-02073-x.

Zhao, Naizhuo, Audrey Smargiassi, Hong Chen, et al. 2025. “Fine Particulate Matter Air Pollution and Anti-Nuclear Antibodies.” Rheumatology (Oxford, England) 65 (1): keaf545. https://doi.org/10.1093/rheumatology/keaf545.