U.S. Department of Veterans Affairs
Date of this Version
Annals of Allergy, Asthma & Immunology, Volume 109, Issue 4, October 2012, Pages 266-273.e2; http://dx.doi.org/10.1016/j.anai.2012.06.015
Background: Organic dust exposure in agricultural environments induces an inflammatory response that attenuates over time, yet repetitive dust exposures result in chronic lung diseases. Animal models resembling this chronic lung inflammatory response have been developed, yet the underlying cellular mechanisms are not well defined.
Objective: Because mice repetitively exposed to organic dust extracts (DE) display increased CD3+ T cell lung infiltrates, we sought to determine the phenotype and importance of these cells.
Methods: Mice received swine confinement DE repetitively for 3 weeks by established intranasal inhalation protocol. Studies were conducted with peptidoglycan (PGN) because it is a major DE component in large animal farming environments and has shared similar biologic effects with DE. Enumeration of T cells and intracellular cytokine profiles were conducted by flow cytometry techniques. Whole lung homogenate cytokines were analyzed by multiplex immunoassay. T cell receptor (TCR) αβ knockouts were used to determine the functional importance of -expressing T cells.
Results: DE increased lung-associated CD3+CD4+ T cells and interleukin (IL)-17 (but not IL-4, interferon [IFN]-γ, IL-10) producing CD4+T cells. PGN treatment resulted in increased IL-17 and IFN- γ producing CD4+ T cells and IFN- γ producing CD8+ T cells. Both DE and PGN augmented expression of cytokines associated with Th1 and Th17 polarization in lung homogenates. DE-induced lung mononuclear aggregates and bronchiolar compartment inflammation were significantly reduced in TCR knockout animals; however, neutrophil influx and alveolar compartment inflammation were not affected.
Conclusion: Studies demonstrated that DE and PGN exposure promote a Th1/Th17 lung microenvironment and that αβ -expressing T cells are important in mediating DE-induced lung pathologic conditions.