Respirable polyethylene terephthalate microplastics modulate airway inflammation and immune responses in murine allergen co-exposure models

• PET MPs are biologically active in vivo • PET MPs show context-, dose-, and allergen-dependent immune modulation • Inhaled PET MPs induce dose-dependent airway inflammation • Systemic PET MPs modulate inflammation and allergen-specific antibodies • PET MPs can exert both adjuvant-like and immunomodulatory effects Polyethylene terephthalate (PET) is a major source of microplastic (MP) exposure through textiles, packaging, and medical devices, yet its immunological effects in controlled experimental models of respiratory and internal exposure remain incompletely characterized. We investigated PET MPs (median 2.7 µm; D90 < 6.5 µm) and their effects in in vivo mouse models of respiratory and intraperitoneal exposure, with and without allergen co-exposure. PET MPs remained detectable in the lung for 14 days, and induced airway inflammation with lymphocyte and eosinophil recruitment. Co-exposure with ragweed pollen amplified pulmonary inflammation at intermediate doses but reduced allergen-specific IgG1 at higher doses. Systemic Intraperitoneal exposure revealed allergen- and timing-dependent modulation of peritoneal inflammation, accompanied by enhanced antibody responses, particularly Th1-associated IgG2a. Splenocyte recall assays showed altered cytokine production. Together, these findings identify PET MPs as biologically active particles that alter airway inflammation and immune responses in a dose- and context-dependent manner under controlled experimental conditions, including high-dose conditions. These findings support the inclusion of immune endpoints while emphasizing the need for cautious extrapolation to real-world exposure scenarios.