Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia.
Oonagh PaerewijckBrecht MaertensLeentje DreesenFrederik Van MeulderIris PeelaersDariusz RatmanRobert W LiErik LubbertsKarolien De BosscherPeter GeldhofPublished in: Scientific reports (2017)
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.
Keyphrases
- rheumatoid arthritis
- immune response
- single cell
- disease activity
- poor prognosis
- ankylosing spondylitis
- transcription factor
- metabolic syndrome
- drug delivery
- adipose tissue
- dna methylation
- interstitial lung disease
- electronic health record
- high fat diet induced
- oxidative stress
- skeletal muscle
- systemic sclerosis
- endothelial cells
- high resolution
- heat stress
- gestational age
- data analysis
- stress induced
- heat shock protein