Exp Mol Med.  2009 Oct;41(10):687-694. 10.3858/emm.2009.41.10.075.

Legionella lipoprotein activates toll-like receptor 2 and induces cytokine production and expression of costimulatory molecules in peritoneal macrophages

• Shim HK
• Kim JY
• Kim MJ
• Sim HS
• Park DW
• Sohn JW
• Kim MJ

• KMID: 1009390
• DOI: http://doi.org/10.3858/emm.2009.41.10.075

Abstract

Legionella bacterium, an intracellular pathogen of mononuclear phagocytes, causes acute fatal pneumonia, especially in patients with impaired cellular immune responses. Until recently, however, the toll-like receptor (TLR) engagement of bacterial proteins derived from Legionella is uncertain. We previously showed that a 19-kDa highly conserved peptidoglycan-associated lipoprotein (PAL) of Legionella pneumophila induced the PAL-specific B cell and T cell responses in mice. In this study, we observed that the rPAL antigen of L. pneumophila, as an effector molecule, activated murine macrophages via TLR2 and produced proinflammatory cytokines such as IL-6 and TNF-alpha. In both BALB/c and TLR4-deficient C3H/HeJ mice, pretreatment of macrophages with anti-TLR2 mAb showed severely impaired cytokine production in response to the rPAL. In addition, in vitro the rPAL treatment increased the cell surface expression of CD40, CD80, CD86 and MHC I/II molecules. We further showed that the synthetic CpG-oligodeoxynucleotides (CpG ODN) coadministered with the rPAL enhanced IL-12 and IL-6 production and expression of CD40, CD80 and MHC II compared to the rPAL treatment alone. In conclusions, these results indicate that Legionella PAL might activate macrophages via a TLR2-dependent mechanism which thus induce cytokine production and expression of costimulatory and MHC molecules.

Keyword

Legionella pneumophila; Legionnaires' disease; lipoproteins; macrophages, peritoneal; Toll-like receptors

MeSH Terms

Animals
Antigens, CD/immunology/metabolism
Bacterial Outer Membrane Proteins/*pharmacology
Cells, Cultured
Female
Histocompatibility Antigens Class II/immunology/metabolism
Host-Pathogen Interactions
Interleukin-12/biosynthesis
Interleukin-6/biosynthesis
Legionella pneumophila/*immunology/metabolism
Legionnaires' Disease/immunology/metabolism
Lipoproteins/*pharmacology
Macrophage Activation/drug effects/immunology
Macrophages, Peritoneal/drug effects/immunology/*metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Toll-Like Receptor 2/*metabolism
Tumor Necrosis Factor-alpha/biosynthesis