Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia

Oonagh Paerewijck,Frederik Van Meulder,Dariusz Ratman,Peter Geldhof,Erik Lubberts,Leentje Dreesen,Robert W Li,Brecht Maertens,Iris Peelaers,Karolien De Bosscher

doi:10.1038/s41598-017-08590-x

Oonagh Paerewijck, Frederik Van Meulder + Show 8 more

Open Access

https://doi.org/10.1038/s41598-017-08590-x

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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 post infection, 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 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 α- and β-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, the polymeric immunoglobulin receptor, 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 Giardia infection.

Highlights

The intestinal protozoan parasite Giardia duodenalis has a wide vertebrate host range with high prevalences found both in production and companion animals
In order to further extend our knowledge on the IL-17A-induced anti-Giardia immune response, in the current study RNA deep sequencing technology was applied as an unbiased way to analyse the intestinal response following a G. muris infection in both C57BL/6 WT and C57BL/6 IL-17 receptor A (IL-17RA) KO mice
Differential expression analysis performed on the sequence reads obtained from C57BL/6 WT infected versus C57BL/6 WT uninfected control mice resulted in the identification of 844 differentially expressed (DE) genes

Summary

Introduction

The intestinal protozoan parasite Giardia duodenalis has a wide vertebrate host range with high prevalences found both in production and companion animals. In order to further extend our knowledge on the IL-17A-induced anti-Giardia immune response, in the current study RNA deep sequencing technology was applied as an unbiased way to analyse the intestinal response following a G. muris infection in both C57BL/6 WT and C57BL/6 IL-17RA KO mice. The outcome of this analysis indicated that a Giardia infection triggered an IL-17RA-dependent transcriptional upregulation of a wide array of antimicrobial proteins and complement factors, which, in combination with an intestinal IgA response seems to be important to confer protection against this parasite

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