The Chlamydia psittaci Inclusion Membrane Protein 0556 Inhibits Human Neutrophils Apoptosis Through PI3K/AKT and NF-κB Signaling Pathways

• Published in: Frontiers in immunology 2021-08, Vol.12, p.694573-694573
• Main Authors: He, Zhangping, Xiao, Jian, Wang, Jianye, Lu, Simin, Zheng, Kang, Yu, Maoying, Liu, Jie, Wang, Chuan, Ding, Nan, Liang, Mingxing, Wu, Yimou
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis Regulatory Proteins - metabolism; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Cells, Cultured; Chlamydia psittaci; Chlamydophila psittaci - immunology; Chlamydophila psittaci - metabolism; CPSIT_0556; hPMN; Humans; Immune Evasion; Immunology; Interleukin-8 - metabolism; Neutrophils - enzymology; Neutrophils - immunology; Neutrophils - pathology; NF-kappa B - metabolism; NF-κB pathway; Phosphatidylinositol 3-Kinase - metabolism; PI3K/AKT pathway; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Transcription Factor RelA - metabolism
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.694573

Inclusion membrane proteins (Incs) play an important role in the structure and stability of chlamydial inclusion and the interaction between 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 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 .