Abstract
The respiratory epithelium is a complex tissue, composed of distinct cells arranged in a pseudostratified architecture that actively participates in the host response to pathogens. However, the role of the airway epithelium in modulating the immune response to Aspergillus fumigatus (Af) is poorly understood. Recognition of Af by human airway epithelial cells (HAEC) leads to transepithelial migration of neutrophils. Using both a human epithelial cell line, NCI-H292, and a fully pseudostratified primary HAEC model grown at air-liquid interface, we demonstrate that purified Af melanin ghosts potently, and actively, inhibits transmigration of neutrophils across the airway epithelium. Af melanin blocks the production of pro-inflammatory neutrophil chemo-attractants, CXCL8 (IL-8) and CXCL1 (Gro-alpha). Melanin does not block either transcription or translation of IL-8 but blocks post-translational secretion of IL-8 by epithelial cells abolishing the transepithelial cytokine gradient. Our results demonstrate that melanin actively down-regulates airway epithelial mediated pro-inflammatory responses toward Aspergillus and reveals a new strategy by which aspergillus evades the immune system.
