TY - JOUR
T1 - Chlamydia trachomatis infection co-operatively enhances HPV E6-E7 oncogenes mediated tumorigenesis and immunosuppression
AU - Challagundla, Naveen
AU - Chrisophe-Bourdon, Jean
AU - Agrawal-Rajput, Reena
N1 - Funding Information:
Authors acknowledge ICMR-SRF for NC fellowship. Authors acknowledge Fund for Improvement of S&T Infrastructure (FIST)-DST, India for flowcytometry instrument support.
Copyright:
© 2022 Elsevier Ltd. All rights reserved.
PY - 2023/2
Y1 - 2023/2
N2 - Chlamydia trachomatis and human papilloma virus (HPV) are the two most common sexually transmitted infections among women. HPV infection can increase the risk of cervical cancer and infertility while C. trachomatis induces pelvic inflammatory disease. Here, we elucidate the molecular conundrum of the co-infection of HPV and C. trachomatis infection and their outcome with respect to cervical cancer. HPV infection was mimicked by overexpression of HPV 16 E6-E7 or using human cervical cell lines SiHa and C33a (with and without HPV 16 respectively). HPV transfected co-infection increased cell proliferation and resistance to H202 and TNFα-induced cell death compared to individual infections. These changes are brought by alteration in the cell cycle proteins (CDK2, CDK6 and Bcl2) and thus increasing the stemness of the epithelial cells as observed by increased colony forming units and CD133 expression. The co-infection also induces change in the mRNA levels of cells which are involved in mesenchymal phenotype. C. trachomatis in presence of E6-E7 overexpression caused cervical epithelial neoplasm in mice with increased Ki67 expression and decreased P53 levels. Stem cell marker, CD133 expression also increased in the cervical tissues of both infected and co-infected group of mice. The cells obtained from the cervix were able to grow continuously in ex vivo cultures. All these results indicate the co-existence of the C. trachomatis and HPV 16 might increase the risk of cervical cancer.
AB - Chlamydia trachomatis and human papilloma virus (HPV) are the two most common sexually transmitted infections among women. HPV infection can increase the risk of cervical cancer and infertility while C. trachomatis induces pelvic inflammatory disease. Here, we elucidate the molecular conundrum of the co-infection of HPV and C. trachomatis infection and their outcome with respect to cervical cancer. HPV infection was mimicked by overexpression of HPV 16 E6-E7 or using human cervical cell lines SiHa and C33a (with and without HPV 16 respectively). HPV transfected co-infection increased cell proliferation and resistance to H202 and TNFα-induced cell death compared to individual infections. These changes are brought by alteration in the cell cycle proteins (CDK2, CDK6 and Bcl2) and thus increasing the stemness of the epithelial cells as observed by increased colony forming units and CD133 expression. The co-infection also induces change in the mRNA levels of cells which are involved in mesenchymal phenotype. C. trachomatis in presence of E6-E7 overexpression caused cervical epithelial neoplasm in mice with increased Ki67 expression and decreased P53 levels. Stem cell marker, CD133 expression also increased in the cervical tissues of both infected and co-infected group of mice. The cells obtained from the cervix were able to grow continuously in ex vivo cultures. All these results indicate the co-existence of the C. trachomatis and HPV 16 might increase the risk of cervical cancer.
KW - Apoptosis
KW - C. trachomatis
KW - Cellular transformation
KW - Cervical cancer
KW - E6-E7
U2 - 10.1016/j.micpath.2022.105929
DO - 10.1016/j.micpath.2022.105929
M3 - Article
C2 - 36565970
SN - 0882-4010
VL - 175
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
M1 - 105929
ER -
