Immune dysregulation and adaptive resilience in response to air pollution

Air pollution is increasingly recognized as an important environmental factor associated with immune dysfunction and disease susceptibility. This narrative review critically synthesizes current evidence on the molecular and cellular mechanisms by which airborne pollutants may alter immune homeostasis and influence adaptive resilience. Particular attention is given to particulate, gaseous, semi-volatile, and biologically derived pollutants, including particulate matter, ozone, nitrogen dioxide, polycyclic aromatic hydrocarbons, metals, wildfire smoke, pollen, and microbial aerosols. The reviewed evidence indicates that pollutant exposure can induce oxidative stress, mitochondrial dysfunction, epithelial barrier injury, inflammatory signaling, epigenetic alterations, and dysregulation of innate and adaptive immune-cell functions. These responses are highly context-dependent and vary according to pollutant composition, concentration, exposure duration, co-exposures, experimental model, and host susceptibility. Human, animal, and in vitro findings further suggest that persistent exposure may impair pathogen defense and alter macrophage, dendritic-cell, neutrophil, T-cell, and regulatory T-cell responses, while epidemiological evidence associates air-pollution exposure with increased susceptibility to infectious, allergic, respiratory, cardiovascular, and selected immune-mediated outcomes. The review also highlights the importance of the exposome, indoor and outdoor exposure environments, pollutant mixtures, and the gut-lung axis in shaping individual vulnerability. In addition, adaptive mechanisms involving antioxidant signaling, autophagy, epithelial repair, immune regulation, and microbiome-associated responses may initially support resilience but may become insufficient under persistent or high-intensity exposure. By integrating pollutant characteristics, target cells, molecular pathways, immune outcomes, and study systems, this review proposes a multidimensional framework for interpreting the potential transition from protective adaptation to maladaptive immune dysregulation and identifies priorities for future mechanistic, translational, and preventive research. Clinical trial registration: Not applicable. This study is a narrative review and does not report on a clinical trial.