Hookworm exposure decreases human papillomavirus uptake and cervical cancer cell migration through systemic regulation of epithelial-mesenchymal transition marker expression

Scientific Reports volume 8, Article number: 11547 (2018)

Brittany-Amber Jacobs1, Alisha Chetty1, William Gordon Charles Horsnell1,2,3Georgia Schäfer1, Sharon Prince4 & Katherine Ann Smith1,5

 

1Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, 7925, South Africa.

2Institute of Microbiology and Infection, University of Birmingham, B15 2TT, Birmingham, UK.

3Le Studium Institute for Advanced Studies Laboratory of Molecular and Experimental Immunology and Neurogenetics, CNRS-University of Orleans, Rue Dupanloup, 45000, Orléans, France.

4Department of Human Biology, University of Cape Town, Cape Town, 7925, South Africa.

5School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.

Correspondence and requests for materials should be addressed to K.A.S. (email: smithk28@cardiff.ac.uk)

Abstract

Persistent infection with human papillomavirus (HPV) is responsible for nearly all new cervical cancer cases worldwide. In low- and middle-income countries (LMIC), infection with helminths has been linked to increased HPV prevalence. As the incidence of cervical cancer rises in helminth endemic regions, it is critical to understand the interaction between exposure to helminths and the progression of cervical cancer. Here we make use of several cervical cancer cell lines to demonstrate that exposure to antigens from the hookworm N. brasiliensis significantly reduces cervical cancer cell migration and global expression of vimentin and N-cadherin. Importantly, N. brasiliensis antigen significantly reduced expression of cell-surface vimentin, while decreasing HPV type 16 (HPV16) pseudovirion internalization. In vivo infection with N. brasiliensis significantly reduced vimentin expression within the female genital tract, confirming the relevance of these in vitro findings. Together, these findings demonstrate that infection with the hookworm-like parasite N. brasiliensis can systemically alter genital tract mesenchymal markers in a way that may impair cervical cancer cell progression. These findings reveal a possible late-stage treatment for reducing cervical cancer progression using helminth antigens.

Keywords

Cervical cancer
Parasitic infection
Published by

Nature