MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells

Storrie, Skye; Longbottom, David; Barlow, Peter G.; Wheelhouse, Nick

Abstract

Background
Waddlia chondrophila (W. chondrophila) is an emerging agent of respiratory and reproductive disease in humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial agents, such as Chlamydia abortus (C. abortus). The current study investigated the growth characteristics and innate immune responses of human and ruminant epithelial cells in response to infection withW. chondrophila.
Methods
Human epithelial cells (HEp2) were infected withW. chondrophila for 24h. CXCL8 release was significantly elevated in each of the cell lines by active-infection with liveW. chondrophila, but not by exposure to UV-killed organisms. Inhibition of either p38 or p42/44 MAPK
significantly inhibited the stimulation of CXCL8 release in each of the cell lines. To determine the pattern recognition receptor through which CXCL8 release was stimulated, wildtype HEK293 cells which express no TLR2, TLR4, NOD2 and only negligible NOD1 were
infected with live organisms. A significant increase in CXCL8 was observed.
Conclusions/Significance
W. chondrophila actively infects and replicates within both human and ruminant epithelial cells stimulating CXCL8 release. Release of CXCL8 is significantly inhibited by inhibition of either p38 or p42/44 MAPK indicating a role for this pathway in the innate immune response toW. chondrophila infection.W. chondrophila stimulation of CXCL8 secretion in HEK293 cells indicates that TLR2, TLR4, NOD2 and NOD1 receptors are not essential to the innate immune response to infection

Citation

Storrie, S., Longbottom, D., Barlow, P. G., & Wheelhouse, N. (2016). MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells. PLOS ONE, 11(3), Article e0152193. https://doi.org/10.1371/journal.pone.0152193

• Journal Article Type: Article
• Acceptance Date: Mar 10, 2016
• Online Publication Date: Mar 22, 2016
• Publication Date: Mar 22, 2016
• Deposit Date: Mar 21, 2016
• Publicly Available Date: Mar 22, 2016
• Journal: PLoS One
• Print ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 3
• Article Number: e0152193
• DOI: https://doi.org/10.1371/journal.pone.0152193
• Keywords: Waddlia chondrophila; MAPK activation; CXCL8 expression; human epithelial cells
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/9711
• Publisher URL: http://dx.doi.org/10.1371/journal.pone.0152193
• Contract Date: Mar 21, 2016