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PKC and PKC differentially regulate Legionella pneumophila-induced GM-CSF

¹ Dept of Internal Medicine/Infectious Diseases and Pulmonary Medicine, ² FORSYS Junior Research Group, Systems Biology of Lung Inflammation, Charité-Universitätsmedizin Berlin, Berlin, and ³ NG5 Pathogenesis of Legionella Infection, Robert Koch-Institut, Wernigerode, Germany.

CORRESPONDENCE: P. D. N'Guessan, Dept of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: dje_philippe.nguessan{at}charite.de

Keywords: Activator protein 1, granulocyte-macrophage colony-stimulating factor, Legionella pneumophila, nuclear factor-B, protein kinase C, toll-like receptor

Received: November 12, 2008
Accepted March 20, 2009

Legionella pneumophila is an important causative agent of severe pneumonia in humans. The human alveolar epithelium is an effective barrier for inhaled microorganisms and actively participates in the initiation of innate host defense. Although secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) is essential for the elimination of invading Legionella spp., mechanisms of Legionella pneumophila-induced release of this cytokine are widely unknown.

In this study, we have demonstrated a toll-like receptor (TLR)2- and TLR5-dependent release of GM-CSF in L. pneumophila-infected human alveolar epithelial cells. GM-CSF secretion was not dependent on the bacteria type II or type IV secretion system. Furthermore, an increase in protein kinase C (PKC) activity, particularly PKC and PKC, was noted. Blocking of PKC and PKC activity or expression, but not of PKCβ, PKC, PKC, PKC, and PKC, significantly reduced the synthesis of GM-CSF in infected cells. While PKC was critical for the initiation of a nuclear factor-B-mediated GM-CSF expression, PKC regulated GM-CSF production via activator protein 1.

Thus, differential regulation of GM-CSF, production by PKC isoforms, contributes to the host response in Legionnaires' disease.