TY - JOUR
T1 - Proinflammatory responses by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum are mainly mediated through the recognition of TLR2/TLR1
AU - Zhu, Jianzhong
AU - Krishnegowda, Gowdahalli
AU - Li, Guangfu
AU - Channe Gowda, D.
N1 - Funding Information:
The study was supported by the grant AI41139 from the National Institute of Infectious Diseases and Allergy , NIH, and funding from the Pennsylvania Department of Health . We thank Drs. Shizuo Akira and Satoshi Uematsu, Research Institute for Microbial Diseases, Osaka University, Japan, for providing TLR gene knockout mice.
PY - 2011/7
Y1 - 2011/7
N2 - The glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum have been shown to activate macrophages and produce inflammatory responses. The activation of macrophages by malarial GPIs involves engagement of Toll like receptor 2 (TLR2) resulting in the intracellular signaling and production of cytokines. In the present study, we investigated the requirement of TLR1 and TLR6 for the TLR2 mediated cell signaling and proinflammatory cytokine production by macrophages. The data demonstrate that malarial GPIs, which contain three fatty acid substituents, preferentially engage TLR2-TLR1 dimeric pair than TLR2-TLR6, whereas their derivatives, sn-2 lyso GPIs, that contain two fatty acid substituents recognize TLR2-TLR6 with slightly higher selectivity as compared to TLR2-TLR1 heteromeric pair. These results are analogous to the recognition of triacylated bacterial and diacylated mycoplasmal lipoproteins, respectively, by TLR2-TLR1 and TLR2-TLR6 dimers, suggesting that the lipid portions of the microbial GPI ligands play essential role in determining their TLR recognition specificity.
AB - The glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum have been shown to activate macrophages and produce inflammatory responses. The activation of macrophages by malarial GPIs involves engagement of Toll like receptor 2 (TLR2) resulting in the intracellular signaling and production of cytokines. In the present study, we investigated the requirement of TLR1 and TLR6 for the TLR2 mediated cell signaling and proinflammatory cytokine production by macrophages. The data demonstrate that malarial GPIs, which contain three fatty acid substituents, preferentially engage TLR2-TLR1 dimeric pair than TLR2-TLR6, whereas their derivatives, sn-2 lyso GPIs, that contain two fatty acid substituents recognize TLR2-TLR6 with slightly higher selectivity as compared to TLR2-TLR1 heteromeric pair. These results are analogous to the recognition of triacylated bacterial and diacylated mycoplasmal lipoproteins, respectively, by TLR2-TLR1 and TLR2-TLR6 dimers, suggesting that the lipid portions of the microbial GPI ligands play essential role in determining their TLR recognition specificity.
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U2 - 10.1016/j.exppara.2011.03.010
DO - 10.1016/j.exppara.2011.03.010
M3 - Article
C2 - 21439957
AN - SCOPUS:79956110876
SN - 0014-4894
VL - 128
SP - 205
EP - 211
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 3
ER -
