TY - JOUR
T1 - Serum-borne lipids amplify TLR-activated inflammatory responses
AU - Sharma, Naveen
AU - Akhade, Ajay Suresh
AU - Ismaeel, Sana
AU - Qadri, Ayub
N1 - Funding Information:
We thank Drs. Rahul Pal, Devinder Sehgal, Pushkar Sharma, Praful Tailor and Chinmay Mukhopadhyay for their valuable inputs in the course of this study, and members of the Ayub laboratory for insightful discussions. This work was supported by the Department of Biotechnology, Government of India, through the National Institute of Immunology. N.S., A.S.A., and S.I. received research fellowships from the Council of Scientific and Industrial Research, Government of India.
Publisher Copyright:
©2020 Society for Leukocyte Biology
PY - 2021/4
Y1 - 2021/4
N2 - TLRs recognize conserved pathogen associated molecular patterns and generate innate immune responses. Several circulating and cell membrane associated proteins have been shown to collaborate with TLRs in sensing microbial ligands and promoting inflammatory responses. Here, we show that serum and serum-borne lipids including lysophosphatidylcholine (LPC) amplify inflammatory responses from intestinal epithelial cells and mononuclear phagocytes primed with microbial TLR ligands. Treatment with the inhibitors of G protein-coupled receptor (GPCR) signaling, suramin, or pertussis toxin (PT), the inhibitor of JNK-MAPK, or knockdown of LPC response-regulating GPCR, G2A, decreases the augmentation brought about by serum or LPC in TLR-induced inflammatory response. In vivo administration of PT or anti-G2A antibody reduces TLR2-activated cytokine secretion. The ability of host lipids to costimulate TLR-generated cellular responses represents a novel pathway for the amplification of innate immunity and inflammation.
AB - TLRs recognize conserved pathogen associated molecular patterns and generate innate immune responses. Several circulating and cell membrane associated proteins have been shown to collaborate with TLRs in sensing microbial ligands and promoting inflammatory responses. Here, we show that serum and serum-borne lipids including lysophosphatidylcholine (LPC) amplify inflammatory responses from intestinal epithelial cells and mononuclear phagocytes primed with microbial TLR ligands. Treatment with the inhibitors of G protein-coupled receptor (GPCR) signaling, suramin, or pertussis toxin (PT), the inhibitor of JNK-MAPK, or knockdown of LPC response-regulating GPCR, G2A, decreases the augmentation brought about by serum or LPC in TLR-induced inflammatory response. In vivo administration of PT or anti-G2A antibody reduces TLR2-activated cytokine secretion. The ability of host lipids to costimulate TLR-generated cellular responses represents a novel pathway for the amplification of innate immunity and inflammation.
KW - G protein-coupled receptor
KW - TLR
KW - lysophosphatidylcholine
KW - serum-borne lipids
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U2 - 10.1002/JLB.3AB0720-241RR
DO - 10.1002/JLB.3AB0720-241RR
M3 - Article
C2 - 32717772
AN - SCOPUS:85088560546
SN - 0741-5400
VL - 109
SP - 821
EP - 831
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 4
ER -