Chlamydia psittaci hypothetical inclusion membrane protein CPSIT_0842 evokes a pro-inflammatory response in monocytes via TLR2/TLR4 signaling pathways

Abstract

Chlamydia psittaci (C. psittaci) is an obligate intracellular pathogen that resides within a membrane-bound compartment known as the inclusion. Upon entering the host cell, Chlamydiae secrete numerous proteins to modify the inclusion membrane. Inclusion membrane (Inc) proteins are important pathogenic factors in Chlamydia and play crucial roles in the growth and development of Chlamydia. In the present study, the C. psittaci protein, CPSIT_0842, was identified and shown to localize to the inclusion membrane. Temporal analysis revealed that CPSIT_0842 is an early expression protein of Chlamydia. Moreover, this protein was shown to induce the expression of pro-inflammatory cytokines IL-6 and IL-8 in human monocytes (THP-1 cells) via the TLR2/TLR4 signaling pathway. CPSIT_0842 increases the expression of TLR2, TLR4, and adaptor MyD88. Suppression of TLR2, TLR4, and MyD88 markedly attenuated CPSIT_0842-induced production of IL-6 and IL-8. MAP kinases and NF-κB, important downstream molecules of TLR receptors in inflammatory signaling pathways, were also confirmed to be activated by CPSIT_0842. CPSIT_0842-induced production of IL-6 was reliant on activation of the ERK, p38, and NF-κB signaling pathways while IL-8 expression was regulated by the ERK, JNK, and NF-κB signaling pathways. Specific inhibitors of these signaling pathways significantly decreased CPSIT_0842-mediated expression of IL-6 and IL-8. Together these findings demonstrate that CPSIT_0842 upregulates the expression of IL-6 and IL-8 via TLR-2/TLR4-mediated MAPK and NF-κB signaling pathways in THP-1 cells. Exploring these molecular mechanisms enhances our understanding of C. psittaci pathogenesis.