Chlamydia trachomatis induces autophagy by p62 in HeLa cell


Chlamydia trachomatis is the most common bacterial pathogen causing sexually transmitted diseases. C. trachomatis infection is closely related to the development of cervical cancer, studies have shown that C. trachomatis can induce host cell autophagy. The autophagy related gene p62 plays an important role in the process of autophagy. To further understand the role of autophagy-associated gene p62 in autophagy of HeLa cells induced by C. trachomatis, p62-silencing cell line, HeLa229-shp62, and control cell line, HeLa229-shNC, were constructed, and a C. trachomatis-infected cell model was established. The autophagosome and C. trachomatis inclusions were observed under electron microscope. The autophagy level of C. trachomatis-infected HeLa cells was detected by Western blot. The results suggested that knockdown of p62 affected neither C. trachomatis infection of HeLa cells nor the initiation of C. trachomatis-induced autophagy, but at 48 h post C. trachomatis infection, autophagy levels were significantly inhibited in p62 silencing host cells. The study demonstrated the important role of p62 in the autophagy induced by C. trachomatis in HeLa cells, which could provide data support and theoretical basis for exploring the pathogenesis and prevention of C. trachomatis.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Data availability

The data supporting the findings of this study are available within the article.


  1. Alegre F, Moragrega AB, Polo M, Marti-Rodrigo A, Esplugues JV, Blas-Garcia A, Apostolova N (2018) Role of p62/SQSTM1 beyond autophagy: a lesson learned from drug-induced toxicity in vitro. Br J Pharmacol 175:440–455.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Al-Younes HM, Brinkmann V, Meyer TF (2004) Interaction of Chlamydia trachomatis serovar L2 with the host autophagic pathway. Infect Immun 72:4751–4762.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Bestebroer J, V’Kovski P, Mauthe M, Reggiori F (2013) Hidden behind autophagy: the unconventional roles of ATG proteins. Traffic 14:1029–1041.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Cuomo F, Altucci L, Cobellis G (2019) Autophagy function and dysfunction: potential drugs as anti-cancer therapy. Cancers (Basel).

    Article  Google Scholar 

  5. Lamark T, Svenning S, Johansen T (2017) Regulation of selective autophagy: the p62/SQSTM1 paradigm. Essays Biochem 61:609–624.

    Article  PubMed  Google Scholar 

  6. Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Lorincz P, Juhasz G (2019) Autophagosome-lysosome fusion. J Mol Biol.

    Article  PubMed  Google Scholar 

  8. Mackern-Oberti JP et al (2017) Male genital tract immune response against Chlamydia trachomatis infection. Reproduction 154:R99–R110.

    CAS  Article  PubMed  Google Scholar 

  9. McKuen MJ, Mueller KE, Bae YS, Fields KA (2017) Fluorescence-reported allelic exchange mutagenesis reveals a role for Chlamydia trachomatis TmeA in invasion that is independent of host AHNAK. Infect Immun.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132.

    CAS  Article  PubMed  Google Scholar 

  11. Netea-Maier RT, Plantinga TS, van de Veerdonk FL, Smit JW, Netea MG (2016) Modulation of inflammation by autophagy: consequences for human disease. Autophagy 12:245–260.

    CAS  Article  PubMed  Google Scholar 

  12. Newman L et al (2015) Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS ONE 10:e0143304.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. O’Connell CM, Ferone ME (2016) Chlamydia trachomatis. Genital Infections. Microb Cell 3:390–403.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Paavonen J (2012) Chlamydia trachomatis infections of the female genital tract: state of the art. Ann Med 44:18–28.

    CAS  Article  PubMed  Google Scholar 

  15. Pachikara N, Zhang H, Pan Z, Jin S, Fan H (2009) Productive Chlamydia trachomatis lymphogranuloma venereum 434 infection in cells with augmented or inactivated autophagic activities. FEMS Microbiol Lett 292:240–249.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Parzych KR, Klionsky DJ (2014) An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal 20:460–473.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Peipert JF (2003) Clinical practice. Genital chlamydial infections. N Engl J Med 349:2424–2430.

    CAS  Article  PubMed  Google Scholar 

  18. Ravanan P, Srikumar IF, Talwar P (2017) Autophagy: the spotlight for cellular stress responses. Life Sci 188:53–67.

    CAS  Article  PubMed  Google Scholar 

  19. Ricci V (2016) Relationship between VacA toxin and host cell autophagy in Helicobacter pylori infection of the human stomach: a few answers. Many Questions Toxins (Basel).

    Article  PubMed Central  Google Scholar 

  20. Sanchez-Martin P, Komatsu M (2018) p62/SQSTM1-steering the cell through health and disease. J Cell Sci.

    Article  PubMed  Google Scholar 

  21. Sharma V, Verma S, Seranova E, Sarkar S, Kumar D (2018) Selective autophagy and xenophagy in infection and disease front cell. Dev Biol 6:147.

    Article  Google Scholar 

  22. Subbarayal P, Karunakaran K, Winkler AC, Rother M, Gonzalez E, Meyer TF, Rudel T (2015) EphrinA2 receptor (EphA2) is an invasion and intracellular signaling receptor for Chlamydia trachomatis. PLoS Pathog 11:e1004846.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Tang W et al (2020) Pregnancy and fertility-related adverse outcomes associated with Chlamydia trachomatis infection: a global systematic review and meta-analysis. Sex Transm Infect 96:322–329.

    Article  PubMed  Google Scholar 

  24. Vergne I, Lafont F, Espert L, Esclatine A, Biard-Piechaczyk M (2017) Autophagy, ATG proteins and infectious diseases. Med Sci (Paris) 33:312–318.

    Article  Google Scholar 

  25. Wang F et al (2019) Inflammatory mechanism of Chlamydia trachomatis-infected HeLa229cells regulated by Atg5. Biochem Biophys Res Commun.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Witkin SS, Minis E, Athanasiou A, Leizer J, Linhares IM (2017) Chlamydia trachomatis: the persistent pathogen. Clin Vaccine Immunol.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yang Y et al (2019) Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response. Nat Commun 10:3759.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Yong EC, Chi EY, Kuo CC (1987) Differential antimicrobial activity of human mononuclear phagocytes against the human biovars of Chlamydia trachomatis. J Immunol 139:1297–1302

    CAS  PubMed  Google Scholar 

  29. Yu P, Xiao L, Lin L, Tang L, Chen C, Wang F, Wang Y (2016) STAT3-mediated TLR2/4 pathway upregulation in an IFN-gamma-induced Chlamydia trachomatis persistent infection model. Pathog Dis.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


This work was supported by National Natural Science Foundation of China (Grant Nos. 81371864, 81572040 and 81501791) and Natural Science Foundation of Hunan Province (2018JJ3819 and 2019JJ40392).

Author information



Corresponding authors

Correspondence to Lei Zhang or Yong Wang.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethics approval

The study was approved by the ethics committee of Xiangya School of medicine, Central South University.

Consent for publication

All the authors have agreed for authorship, read and approved the manuscript, and given consent for publication of the manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, F., Zhang, H., Lu, X. et al. Chlamydia trachomatis induces autophagy by p62 in HeLa cell. World J Microbiol Biotechnol 37, 50 (2021).

Download citation


  • Autophagy
  • Autophagosome
  • Chlamydia trachomatis
  • p62