Schmeck B, N'Guessan PD, Ollomang M, Lorenz J, Zahlten J, Opitz B, Flieger A, Suttorp N, Hippenstiel S (2007): Legionella pneumophila induced NF-κB- and MAP kinase-dependent cytokine release by alveolar epithelial cells
Eur. Respir. J. 29 (1): 25-33, Epub ahead of print 2006 Sep 13. doi:10.1183/09031936.00141005.

Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with alveolar epithelium. We tested whether L. pneumophila-infection of lung epithelial cells (A549) resulted in proinflammatory activation.

L. pneumophila-infection induced liberation of IL-2, IL-4, IL-6, IL-8, IL-17, MCP-1, TNFα, IL-1β, IFNγ, G-CSF, but not of IL-5, IL-7, IL-10, IL-12 (p70), IL-13 or GM-CSF. We focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby, and to a lower extent, JR32. Knock out of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 MAP kinase was activated and kinase inhibition reduced secretion of of induced cytokines with exception of IL-2 and G-CSF. In contrast, inhibition of MEK1/ERK pathway only reduced expression of few cytokines. L. pneumophila also induced binding of NF-κB subunit RelA/p65 and the RNA polymerase II to the il8 promoter and a specific inhibitor of the IκBα- complex dose-dependently lowered IL-8 expression.

Taken together, L. pneumophila activated p38 MAP kinase- and NF-κB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to immune response in Legionellosis.