Toll-like receptor 2 (TLR2) and dectin-1 contribute to the production of IL-12p40 by bone marrow-derived dendritic cells infected with Penicillium marneffei.
The present study was designed to elucidate the role of TLR2, TLR4 and dectin-1 in the production of IL-12p40 by bone marrow-derived dendritic cells (BM-DCs) infected with Penicillium marneffei. IL-12p40 production was almost completely abrogated in BM-DCs from TLR2 gene-knockout (KO) and MyD88KO mice, but not from TLR4-defective C3H/HeJ mice compared to those from control mice. Furthermore, BM-DCs from dectin-1KO mice faintly produced IL-12p40 upon stimulation with this fungus. Using a luciferase reporter assay, P. marneffei activated NF-kappaB in HEK293 cells transfected with the TLR2 gene, but not with the dectin-1 gene, and their co-transfection did not lead to further increase in this response. These results indicate that TLR2 and dectin-1 are essential in sensing P. marneffei for the activation of BM-DCs.
Nakamura
Kiwamu
K
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Miyazato
Akiko
A
Koguchi
Yoshinobu
Y
Adachi
Yoshiyuki
Y
Ohno
Naohito
N
Saijo
Shinobu
S
Iwakura
Yoichiro
Y
Takeda
Kiyoshi
K
Akira
Shizuo
S
Fujita
Jiro
J
Ishii
Keiko
K
Kaku
Mitsuo
M
Kawakami
Kazuyoshi
K
D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis*; D037181:Lectins, C-Type; D008156:Luciferases; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010407:Penicillium / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D000099181:Dectin-1
D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D008156:Luciferases; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000099181:Dectin-1