Alveolar macrophage phenotypes in severe equine asthma

Area of Science:

• Veterinary Immunology
• Equine Respiratory Diseases
• Cellular Biology

Background:

• Alveolar macrophages (AMs) play a crucial role in respiratory health.
• The phenotype of AMs in horses with severe equine asthma (SEA) remains poorly understood.
• Understanding AM polarization is key to addressing inflammatory lung conditions in horses.

Purpose of the Study:

• To characterize M1- and M2-polarized AM phenotypes in horses.
• To test the hypothesis that natural hay/straw challenge (NC) induces divergent AM phenotypes in control horses versus horses with SEA.
• To investigate the role of cytokines and pathogen-associated molecular patterns (PAMPs) in AM responses.

Main Methods:

• AMs from control horses were polarized to M1 or M2 phenotypes using specific stimuli (eIFNγ + LPS or eIL-4).
• Gene expression of polarized AMs was analyzed in response to various PAMPs (LPS, zymosan, peptidoglycan, hay dust).
• AM gene expression was compared between control horses and horses with SEA at pasture and after NC.

Main Results:

• M1 polarization upregulated pro-inflammatory cytokines and CD80; M2 polarization upregulated CD206 and downregulated arginase-II and IL-10.
• SEA horses exhibited consistently elevated IL-10 expression in AMs, both at pasture and post-NC.
• NC induced a temporary increase in IL-10 in control horses, highlighting a diminished dynamic response in SEA horses.

Conclusions:

• Horses with SEA display a fundamental shift in AM phenotype, characterized by elevated IL-10 production.
• AMs in SEA horses appear to have lost the ability to respond dynamically to environmental cues, unlike control horses.
• These findings provide insights into the immunopathology of SEA and potential therapeutic targets.