TY - JOUR
T1 - Limited contribution of Toll-like receptor 2 and 4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans
AU - Nakamura, Kiwamu
AU - Miyagi, Kazuya
AU - Koguchi, Yoshinobu
AU - Kinjo, Yuki
AU - Uezu, Kaori
AU - Kinjo, Takeshi
AU - Akamine, Morikazu
AU - Fujita, Jiro
AU - Kawamura, Ikuo
AU - Mitsuyama, Masao
AU - Adachi, Yoshiyuki
AU - Ohno, Naohito
AU - Takeda, Kiyoshi
AU - Akira, Shizuo
AU - Miyazato, Akiko
AU - Kaku, Mitsuo
AU - Kawakami, Kazuyoshi
PY - 2006/6
Y1 - 2006/6
N2 - The present study was designed to elucidate the role of Toll-like receptor (TLR) 2 and TLR4 in the host response to Cryptococcus neoformans. Both TLR2 knockout (KO) and TLR4KO mice produced interleukin-1β (IL-1β), IL-6, IL-12p40 and tumor necrosis factor-α (TNF-α) in sera and cleared this fungal pathogen from infected lungs at a comparable level to control littermate (LM) mice. Synthesis of these cytokines was not significantly different in the lungs of these KO mice and LM mice, although IL-1β, IL-6 and IL-12p40 tended to be lower in TLR2KO, but not TLR4KO, mice than in controls. In addition, there was no significant reduction detected in the synthesis of IL-12 and TNF-α by bone marrow-derived dendritic cells from TLR2KO and TLR4KO mice upon stimulation with live yeast cells. Finally, HEK293 cells expressing either TLR2/dectin-1 or TLR4/MD2/CD14 did not respond to C. neoformans in the activation of nuclear factor kappa B (NFκB) detected by a luciferase assay. Our results suggest that TLR2 and TLR4 do not or only marginally contribute to the host and cellular response to this pathogen.
AB - The present study was designed to elucidate the role of Toll-like receptor (TLR) 2 and TLR4 in the host response to Cryptococcus neoformans. Both TLR2 knockout (KO) and TLR4KO mice produced interleukin-1β (IL-1β), IL-6, IL-12p40 and tumor necrosis factor-α (TNF-α) in sera and cleared this fungal pathogen from infected lungs at a comparable level to control littermate (LM) mice. Synthesis of these cytokines was not significantly different in the lungs of these KO mice and LM mice, although IL-1β, IL-6 and IL-12p40 tended to be lower in TLR2KO, but not TLR4KO, mice than in controls. In addition, there was no significant reduction detected in the synthesis of IL-12 and TNF-α by bone marrow-derived dendritic cells from TLR2KO and TLR4KO mice upon stimulation with live yeast cells. Finally, HEK293 cells expressing either TLR2/dectin-1 or TLR4/MD2/CD14 did not respond to C. neoformans in the activation of nuclear factor kappa B (NFκB) detected by a luciferase assay. Our results suggest that TLR2 and TLR4 do not or only marginally contribute to the host and cellular response to this pathogen.
KW - Cryptococcus neoformans
KW - Dectin-1
KW - Host response
KW - TLR2
KW - TLR4
UR - http://www.scopus.com/inward/record.url?scp=33646720675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646720675&partnerID=8YFLogxK
U2 - 10.1111/j.1574-695X.2006.00078.x
DO - 10.1111/j.1574-695X.2006.00078.x
M3 - Article
C2 - 16706798
AN - SCOPUS:33646720675
VL - 47
SP - 148
EP - 154
JO - Pathogens and Disease
JF - Pathogens and Disease
SN - 2049-632X
IS - 1
ER -
