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

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

Authors

Skye Storrie

David Longbottom



Contributors

David M. Ojcius
Editor

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

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

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MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells (1.2 Mb)
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
© 2016 Storrie et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.





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