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

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

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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