Organic dust exposure in the agricultural industry results in significant airway disease and lung function decline. Mononuclear phagocytes are key cells that mediate the inflammatory and innate immune response following dust exposure.
To investigate the effect of organic dust extract (ODE) from modern swine operations on monocyte-derived macrophage (MDM) phenotype and function.
Peripheral blood monocytes were obtained by elutriation methodology (>99% mCD14+) and differentiated into macrophages in the presence of GM-CSF (1 week) with and without ODE (0.1%). At one week, cells were analyzed by flow cytometry for cell surface marker expression (HLA-DR, CD80, CD86, TLR2, TLR4, mCD14, CD16), phagocytosis (IgG-opsonized zymosan particles), and intracellular killing of Streptococcus pneumoniae. At one week, MDMs were re-challenged with high dose ODE (1%), lipopolysaccharide (LPS), and peptidoglycan (PGN), and cytokines (TNFα, IL-6, IL-10, CXCL8/IL-8) were measured. To elucidate ODE-associated factors, comparisons were made to MDMs conditioned with heat-inactivated dust, endotoxin-depleted dust, LPS, and PGN.
Expression of HLA-DR, CD80, CD86, phagocytosis and intracellular bacterial killing were significantly decreased with ODE- versus control-MDMs. Responses were retained after marked depletion of endotoxin. PGN, LPS and PGN + LPS significantly reduced MDM surface marker expression, and except for LPS alone, also reduced phagocytosis. ODE-MDMs had significantly diminished cytokine responses (TNFα, IL-6, IL-10) following repeat challenge with high dose ODE. Cross-tolerant cytokine responses were also observed.
Repetitive organic dust exposure significantly decreases markers of antigen presentation and host defense function in monocyte-derived macrophages. Bacterial cell components appear to be driving these impaired responses.
Repetitive organic dust exposure impairs monocyte-derived macrophage host defense functions.
Gram positive bacterial cell components may be driving this impaired response.
Clinical implications: Organic dust-induced macrophage dysfunction may be important in respiratory disease development.
Repetitive organic dust exposure in vitro impairs host defense function in monocyte-derived macrophages, which appear to be driven by gram positive bacterial cell components. Organic dust-induced macrophage dysfunction may be important in respiratory disease development.