Abstract
Inclusion membrane proteins (Incs) play an important role in the structure and stability of chlamydial inclusion and the interaction between Chlamydia spp. and their hosts. Following Chlamydia infection through the respiratory tract, human polymorphonuclear neutrophils (hPMN) not only act as the primary immune cells reaching the lungs, but also serve as reservoir for Chlamydia. We have previously identified a Chlamydia psittaci hypothetical protein, CPSIT_0556, as a medium expressed inclusion membrane protein. However, the role of inclusion membrane protein, CPSIT_0556 in regulating hPMN functions remains unknown. In the present study, we found that CPSIT_0556 could not only inhibit hPMN apoptosis through the PI3K/Akt and NF-κB signaling pathways by releasing IL-8, but also delays procaspase-3 processing and inhibits caspase-3 activity in hPMN. Up-regulating the expression of anti-apoptotic protein Mcl-1 and down-regulating the expression of pro-apoptotic protein Bax could also inhibit the translocalization of Bax in the cytoplasm into the mitochondria, as well as induce the transfer of p65 NF-κB from the cytoplasm to the nucleus. Overall, our findings demonstrate that CPSIT_0556 could inhibit hPMN apoptosis through PI3K/Akt and NF-κB pathways and provide new insights towards understanding a better understanding of the molecular pathogenesis and immune escape mechanisms of C. psittaci.
Highlights
C. psittaci is a zoonotic pathogen that can cause respiratory and digestive diseases in birds, as well as severe pneumonia and bacteremia in humans
To investigate whether the inclusion membrane protein CPSIT_0556 of C. psittaci can inhibit the apoptosis of human polymorphonuclear neutrophils (hPMN), we evaluated the expression of B-cell lymphoma 2 (Bcl-2) associated X protein (Bax) and Mcl-1 following CPSIT_0556 culture with stimulated hPMN at different concentrations and at different timepoints
When Chlamydia pneumoniae invade the hPMN, the inclusion formed by elementary body (EB) and reticulate body (RB) in hPMN differed from those formed on invasion of epithelial cells, but were similar to those observed monocytes [62], which suggested that inclusion formation is an important mechanism used by Chlamydia to escape hPMN killing
Summary
C. psittaci is a zoonotic pathogen that can cause respiratory and digestive diseases in birds, as well as severe pneumonia and bacteremia in humans. Transmission occurs through the respiratory tract to other tissues, and may present as a severe systemic infection, which ranges from mild to severe [1]. The entry of extracellular infectious EB into host cells is most likely initiated by the induction of endocytosis [2]. Upon entry into host cells, the EB differentiates into a non-infectious but metabolically active reticulum (RB). The progeny RBs differentiate again into EBs and spread to neighboring cells, restarting the infectious cycle [3]. EB and RB are membranebound and form various types of inclusion bodies in host cells [4]. Our group identified CPSIT_0556 as a metaphase expressed protein, located in the inclusion membrane, and has the same structural characteristics as CPSIT_0844 and CPSIT_0846 [6]
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