Urban PM2.5 exacerbates allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway

Area of Science:

• Immunology
• Environmental Health
• Pulmonology

Background:

• Particulate matter 2.5 (PM2.5) is known to worsen asthma, but its precise mechanism remains unclear.
• Toll-like receptors (TLRs) are crucial in immune responses to microbial components often found on PM2.5.

Purpose of the Study:

• To investigate the role of toll-like receptor (TLR) 2, TLR4, and MyD88 in PM2.5-exacerbated allergic lung inflammation.
• To elucidate the signaling pathway involved in PM2.5-induced exacerbation of allergen-induced eosinophilia.

Main Methods:

• Wild-type (WT) and gene-deficient (TLR2-/-, TLR4-/-, MyD88-/-) BALB/c mice were challenged with PM2.5 and/or ovalbumin (OVA).
• Lung inflammation, including eosinophil counts, cytokine levels (IL-5, IL-13), and immune cell infiltration, were assessed.
• Serum levels of antigen-specific IgE and IgG1 were measured.

Main Results:

• PM2.5 alone increased neutrophils and KC in bronchoalveolar lavage fluid and caused mild lung inflammation in WT mice.
• PM2.5 exacerbated OVA-induced lung eosinophilia, characterized by increased eosinophils, goblet cell proliferation, and elevated IL-5, IL-13, eotaxin, MCP-3, IgE, and IgG1.
• These exacerbations were significantly attenuated in TLR2-/-, TLR4-/-, and particularly MyD88-/- mice, with negligible pathology in the latter.
• PM2.5-bound microbial elements like LPS are potential contributors.

Conclusions:

• Urban PM2.5 exacerbates allergic lung inflammation in mice through a TLR2/TLR4/MyD88 signaling pathway.
• MyD88 plays a critical role in mediating PM2.5-induced allergic airway inflammation.
• Microbial components adsorbed onto PM2.5 may be key drivers of lung eosinophilia exacerbation.