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

Sci Rep. 2017 Aug 17;7(1):8520. doi: 10.1038/s41598-017-08590-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Complement Activation
  • Complement System Proteins / metabolism
  • Disease Models, Animal
  • Gene Expression Profiling
  • Giardia / immunology*
  • Giardiasis / immunology*
  • Giardiasis / pathology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-17 / deficiency
  • Receptors, Interleukin-17 / metabolism*
  • Receptors, Polymeric Immunoglobulin / metabolism
  • Sequence Analysis, RNA
  • Signal Transduction

Substances

  • Antimicrobial Cationic Peptides
  • Receptors, Interleukin-17
  • Receptors, Polymeric Immunoglobulin
  • Complement System Proteins