|PAEREWIJCK, OONAGH - Ghent University|
|PEELAERS, IRIS - Ghent University|
|MAERTENS, BRECHT - Ghent University|
|DREESEN, LEENTJE - Ghent University|
|VAN MEULDER, FREDERIK - Ghent University|
|DE BOSSCHER, KAROLIEN - Ghent University|
|GELDHOF, PETER - Ghent University|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/12/2017
Publication Date: 8/17/2017
Citation: Paerewijck, O., Peelaers, I., Maertens, B., Dreesen, L., Van Meulder, F., De Bosscher, K., Li, R.W., Geldhof, P. 2017. Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia. Scientific Reports. 7:8520. https://doi.org/10.1038/s41598-017-08590-x.
Interpretive Summary: Approximately 280 million people each year are infected with intestinal protozoan parasites in the genus Giardia. It would be highly desirable to achieve effective vaccines given the high prevalence of these infections in production and companion animals, and given their impact on public health. However, current Giardia vaccines have not been effective, especially against asymptomatic infections in companion animals. In this study, we dissected a critical role for a signaling pathway (IL-17A) in eliciting protective immune responses against Giardia by determining a cascade of genes whose expression, after infection, is mediated by this molecule. Our findings will facilitate the development of the more efficacious vaccines, which could bring major benefits to agriculture, animal health, and public health.
Technical Abstract: The protozoan parasite Giardia is a highly prevalent intestinal pathogen with a wide host range. Data obtained in mice, cattle and humans revealed the importance of IL-17A in the development of a protective immune response against Giardia. The aim of this study was to further unravel the protective effector mechanisms triggered by IL-17A following G. muris infection in mice by an RNA-sequencing approach. C57Bl/6 WT and C57Bl/6 IL-17RA KO mice were orally infected with G. muris cysts. Three weeks postinfection, intestinal tissue samples were collected for RNA-sequencing, with samples from uninfected C57Bl/6 WT and C57Bl/6 IL-17RA KO animals serving as negative controls. Differential expression analysis showed that a G. muris infection evoked the transcriptional upregulation of a wide array of genes, mainly in animals with competent IL-17RA signaling. IL-17RA signaling induced the production of various antimicrobial peptides, such as angiogenin 4 and a- and ß-defensins and regulated complement activation through mannose-binding lectin 2. The expression of the receptor that regulates the secretion of IgA into the intestinal lumen was also dependent on IL-17RA signaling. Interestingly, the transcriptome data showed for the first time the involvement of the circadian clock in the host response following a Giardia infection.