Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures

Abstract

Exposure to agriculture organic dusts, comprised of a diversity of pathogen-associated molecular patterns, results in chronic airway diseases. The multi-functional class A macrophage scavenger receptor (SRA)/CD204 has emerged as an important class of pattern recognition receptors with broad ligand binding ability. The objective was to determine the role of SRA in mediating repetitive and post-inflammatory organic dust extract (ODE)-induced airway inflammation. Wild-type (WT) and SRA knockout (KO) mice were intra-nasally treated with ODE or saline daily for 3 weeks and immediately euthanized or allowed to recover for 1 week. Results show that lung histopathologic changes were increased in SRA KO mice as compared to WT following repetitive ODE exposures marked predominately by increased size and distribution of lymphoid aggregates. After a 1-week recovery from daily ODE treatments, there was significant resolution of lung injury in WT mice, but not SRA KO animals. The increased lung histopathology induced by ODE treatment was associated with decreased accumulation of neutrophils, but greater accumulation of CD4⁺ T-cells. The lung cytokine milieu induced by ODE was consistent with a T_H1/T_H17 polarization in both WT and SRA KO mice. Overall, the data demonstrate that SRA/CD204 plays an important role in the normative inflammatory lung response to ODE, as evidenced by the enhanced dust-mediated injury viewed in the absence of this receptor.

• Farm
• inflammation
• lung
• lymphocyte
• toll-like receptor
• T_H17

Acknowledgements

The authors wish to thank Jane DeVasure, Jackie Pavlik, and Christopher Bauer for technical assistance, and David Wert, Facility Supervisor, Pathology and Microbiology Department in the UNMC Tissue Science Facility for assistance with lung tissue processing, sectioning, H&E staining, and assistance with digital microscopy images prepared for the manuscript. We also thank Charles A. Kuszynski, PhD (Scientific Director) and Victoria B. Smith (Cytometer Operator) with the UNMC Cell Analysis Facility for assistance with flow cytometry analysis, and Lisa Chudomelka for assistance in the manuscript preparation.