Molecular mechanism underlying the TLR4 antagonistic and antiseptic activities of papiliocin, an insect innate immune response molecule

  • Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2115669119. doi: 10.1073/pnas.2115669119.
Manigandan Krishnan  1 ,  Joonhyeok Choi  1 ,  Ahjin Jang  1 ,  Sungjae Choi  1 ,  Jiwon Yeon  1 ,  Mihee Jang  1 ,  Yeongjoon Lee  1 ,  Kkabi Son  1 ,  Soon Young Shin  2 ,  Myeong Seon Jeong  3 ,  Yangmee Kim  1
Affiliations
  • 1. Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, South Korea.
  • 2. Department of Biological Sciences, Konkuk University, Seoul 05029, South Korea.
  • 3. Chuncheon Center, Korea Basic Science Institute, Chuncheon 24341, South Korea.
PMID: 35238667 DOI: 10.1073/pnas.2115669119
Abstract

SignificanceSimilar to mammalian TLR4/MD-2, the Toll9/MD-2-like protein complex in the silkworm, Bombyx mori, acts as an innate pattern-recognition receptor that recognizes lipopolysaccharide (LPS) and induces LPS-stimulated expression of antimicrobial peptides such as cecropins. Here, we report that papiliocin, a cecropin-like insect antimicrobial peptide from the swallowtail butterfly, competitively inhibits the LPS-TLR4/MD-2 interaction by directly binding to human TLR4/MD-2. Structural elements in papiliocin, which are important in inhibiting TLR4 signaling via direct binding, are highly conserved among insect cecropins, indicating that its TLR4-antagonistic activity may be related to insect Toll9-mediated immune response against microbial Infection. This study highlights the potential of papiliocin as a potent TLR4 Antagonist and safe peptide Antibiotic for treating gram-negative sepsis.

Keywords
LPS; Toll-like receptor 4; antimicrobial peptide; insect cecropin; insect innate immunity.
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