Legionella lipoprotein activates toll-like receptor 2 and induces cytokine production and expression of costimulatory molecules in peritoneal macrophages.
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.
Shim
Ho Ki
HK
Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul 136-705, Korea.
Kim
Jeoung Yeon
JY
Kim
Mi Jeong
MJ
Sim
Hee Sun
HS
Park
Dae Won
DW
Sohn
Jang Wook
JW
Kim
Min Ja
MJ
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016952:Legionella pneumophila / Q000276:immunology* / Q000378:metabolism; D007877:Legionnaires' Disease / Q000276:immunology / Q000378:metabolism; D008074:Lipoproteins / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D008074:Lipoproteins; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12