100252 - Particulate Matter Co-Exposure with Indoor Airborne Bacteria Synergistically Exacerbates Allergic Rhinitis and Pulmonary Toxicity in Mice

Indoor air pollution is characterized by simultaneous exposure to multiple hazardous factors. While particulate matter (PM) and airborne microorganisms are individually recognized as contributors to respiratory disease, the combined toxicological effects of their co-exposure in models of allergic airway disease remain insufficiently understood.

In this study, we investigated whether PM and environmentally-derived bacteria act synergistically to exacerbate allergic rhinitis (AR) symptoms and induce pulmonary injury beyond the levels observed with either agent alone.

An OVA-induced allergic rhinitis (AR) mouse model was established in C57BL/6 mice via intraperitoneal sensitization with OVA (50 μg) and alum (1 mg) on Days 0, 7, and 14, followed by intranasal challenge with OVA (100 μg) on Days 21–24. During the challenge period, three dominant indoor airborne bacterial species — Kocuria palustris (B39), Micrococcus yunnanensis (B53), and Moraxella osloensis (B54) — were administered intranasally either alone or in combination with carbon-core PM₂.₅ (100 μg/20 μL) at 10⁵ CFU/20 μL, yielding a total of 9 experimental groups (N=5 per group). Primary outcome measures focused on toxicity and disease exacerbation, including nasal scratching frequency, complete blood count (CBC), and serum biochemical markers of organ stress — aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK). Results were interpreted in the context of a comparative repeated intratracheal instillation model (N=6 per group), in which co-exposure to PM with Bifidobacterium infantis and Bjerkandera adusta was evaluated.

Co-exposure to PM abolished residual nasal immune responses across all bacterial groups, with symptom severity reaching or exceeding that of the OVA challenge control. Systemic tissue injury markers — AST, LDH, and CK — were synergistically elevated in all bacteria+PM co-exposure groups, significantly surpassing levels observed with PM or bacteria alone (p<0.05). The most pronounced elevations were detected in the K. palustris+PM and M. yunnanensis+PM groups, with LDH and CK increasing 3- to 8-fold relative to controls.

Hematological analyses revealed PM-driven immune dysregulation. Despite symptomatic exacerbation, peripheral eosinophil counts declined, suggesting increased tissue-level eosinophil trafficking, while reactive thrombocytosis (~3-fold over OVA control) was observed across all PM-containing groups, reflecting systemic vascular and inflammatory activation. Notably, the M. osloensis+PM group exhibited marked neutrophilia, indicative of a shift from Th2-dominant toward neutrophilic innate immune responses and a synergistic LPS–PM immunopathological mechanism. Collectively, these findings demonstrate that simultaneous exposure to PM and indoor microorganisms elicits pathway-specific immunotoxic synergy that exceeds simple additive effects.

Co-exposure to PM and indoor airborne bacteria synergistically induced multi-organ tissue injury (elevated AST, LDH, CK) and drove a shift from Th2-dominant mucosal inflammation toward innate immunity-based immunopathology, demonstrating pathway-specific synergistic immunotoxicity beyond simple additive effects.