Engagement of Fas on macrophages modulates poly I:C induced cytokine production with specific enhancement of IP-10

Thumbnail Image
CL_EngagementPV2015.pdf(714.05 KB)
Published version
Lyons, Caitríona M.
Fernandes, Philana
Fanning, Liam J.
Houston, Aileen M.
Brint, Elizabeth K.
Journal Title
Journal ISSN
Volume Title
Public Library of Science
Research Projects
Organizational Units
Journal Issue
Viral double-stranded RNA (dsRNA) is recognised by pathogen recognition receptors such as Toll-Like Receptor 3 (TLR3) and retinoic acid inducible gene-I (RIG-I), and results in cytokine and interferon production. Fas, a well characterised death receptor, has recently been shown to play a role in the inflammatory response. In this study we investigated the role of Fas in the anti-viral immune response. Stimulation of Fas on macrophages did not induce significant cytokine production. However, activation of Fas modified the response of macrophages to the viral dsRNA analogue poly I:C. In particular, poly I:C-induced IP-10 production was significantly enhanced. A similar augmentation of IP-10 by Fas was observed following stimulation with both poly A:U and Sendai virus. Fas activation suppressed poly I:C-induced phosphorylation of the MAP kinases p38 and JNK, while overexpression of the Fas adaptor protein, Fas-associated protein with death domain (FADD), activated AP-1 and inhibited poly I:C-induced IP-10 production. Consistent with an inhibitory role for AP-1 in IP-10 production, mutation of the AP-1 binding site on the IP-10 promoter resulted in augmented poly I:C-induced IP-10. These results demonstrate that engagement of the Fas receptor plays a role in modifying the innate immune response to viral RNA.
NF-kappaB , Domain-containing protein , Hepatitis C virus , RIG-I , Death domain , Induced apoptosis , Infected cells , Activation , Fadd , IL-1 beta
Lyons C, Fernandes P, Fanning LJ, Houston A, Brint E (2015) Engagement of Fas on Macrophages Modulates Poly I:C Induced Cytokine Production with Specific Enhancement of IP-10. PLoS ONE 10(4): e0123635. doi:10.1371/journal.pone.0123635
Link to publisher’s version