PKC and differentially regulate Legionella pneumophila induced GM-CSF

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

^* To whom correspondence should be addressed. E-mail: dje_philippe.nguessan{at}charite.de.

	Abstract

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, mechanisms of Legionella pneumophila-induced release of this cytokine are widely unknown.

In this study we demonstrated a TLR2- and TLR5-dependent release of GM-CSF in Legionella pneumophila-infected human alveolar epithelial cells. GM-CSF secretion was not dependent on the bacteria type II or IV secretion system. Furthermore, an increase in Protein Kinase C (PKC) activity, particularly PKC and , was noted. Blocking of PKC and PKC activity or expression but not of PKC, PKC, PKC, PKC, and PKC significantly reduced the synthesis of GM-CSF in infected cells. While PKC was critical for the initiation of an NF-B-mediated GM-CSF expression, PKC regulated GM-CSF production via AP1.

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

Keywords:  AP-1, GM-CSF, Legionella pneumophila, NF-B, PKC, TLR