Chlamydia trachomatis glycogen synthase promotes MAPK-mediated proinflammatory cytokine production via TLR2/TLR4 in THP-1 cells

Aims: To investigate the roles and mechanisms of C. trachomatis glycogen synthase (GlgA) in regulating the inflammatory response in THP-1 cells.

Main methods: In this work, after THP-1 cells were stimulated with GlgA, transcript and protein expression levels were measured by qRT-PCR and ELISA, respectively. Western blotting and immunofluorescence were used to determine the signaling pathway involved in the inflammatory mechanism.

Key findings: GlgA elicited the expression of interleukin-8 (IL-8), interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in THP-1 cells, and the blockade of TLR2 and TLR4 signaling abrogated the induction of IL-8, TNF-α and IL-1β expression. Similarly, IL-8, IL-1β and TNF-α secretion was reduced by transfection with a dominant negative plasmid (pDeNyhMyD88). Moreover, Western blotting and immunofluorescence experiments further validated that MAPKs and NF-кB signaling are involved in the transcription and translation of these cytokines. Treatment of the cells with ERK and JNK inhibitors dramatically attenuated the induction of IL-8, IL-1β and TNF-α.

Significance: These results suggest that GlgA contributes to inflammation during C. trachomatis infection via the TLR2, TLR4 and MAPK/NF-кB pathways, which may enhance our understanding of the pathogenesis of C. trachomatis.