Chlamydial plasmid-encoded virulence factor Pgp3 interacts with human cathelicidin peptide LL-37 to modulate immune response

Shuping Hou, Xin Sun, Xiaohua Dong, Hui Lin, Lingli Tang, Min Xue, Guangming Zhong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have previously reported that Chlamydia trachomatis plasmid-encoded Pgp3 is able to neutralize anti-chlamydial activity of human cathelicidin peptide LL-37 by binding to and forming stable complex with LL-37. Besides its microbicidal activity, LL-37 also modulates immune response, including inducing cytokine/chemokine production in fibroblast/epithelial cells and recruitment of inflammatory cells. We now report that LL-37 was significantly induced in the genital tracts of women diagnosed positive for C. trachomatis. Both the LL-37-stimulated IL-6/8 production in human endometrial epithelial cells and the LL-37-induced neutrophil chemotaxis were blocked by Pgp3. Interestingly, although Pgp3 itself alone could not induce cytokines in epithelial cell cells, it did so in neutrophils. Importantly, the Pgp3 proinflammatory activity in neutrophils was significantly enhanced by forming complex with LL-37 although LL-37 alone failed to induce cytokine production in neutrophils. Thus, we have demonstrated that Pgp3 can modulate the proinflammatory activities of LL-37 on epithelial cells by forming stable complex with LL-37 but the Pgp3's own proinflammatory activity on myeloid cells is enhanced by forming the same complex. We hypothesize that Chlamydia may use Pgp3 to both block detrimental inflammation for improving its own fitness in the genital tract epithelial tissue and activate myeloid cell-mediated inflammation for potentially promoting spreading between the hosts, the latter of which may inevitably contribute to the development of inflammatory sequelae such as tubal fibrosis.

Original languageEnglish (US)
JournalMicrobes and Infection
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Virulence Factors
Neutrophils
Plasmids
Epithelial Cells
Peptides
Chlamydia trachomatis
Myeloid Cells
Cytokines
Inflammation
Chlamydia
Chemotaxis
Interleukin-8
Chemokines
Human Activities
Interleukin-6
Fibrosis
Epithelium
Fibroblasts
CAP18 lipopolysaccharide-binding protein

Keywords

  • Antimicrobial peptides
  • Chemotaxis
  • Cytokines
  • Fibrosis
  • LL-37
  • Pgp3

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Chlamydial plasmid-encoded virulence factor Pgp3 interacts with human cathelicidin peptide LL-37 to modulate immune response. / Hou, Shuping; Sun, Xin; Dong, Xiaohua; Lin, Hui; Tang, Lingli; Xue, Min; Zhong, Guangming.

In: Microbes and Infection, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Lin, Hui

AU - Tang, Lingli

AU - Xue, Min

AU - Zhong, Guangming

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