RGD Reference Report - Interleukin-18 Mediates Immune Responses to Campylobacter jejuni Infection in Gnotobiotic Mice. - Rat Genome Database

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Interleukin-18 Mediates Immune Responses to Campylobacter jejuni Infection in Gnotobiotic Mice.

Authors: Bereswill, Stefan  Alutis, Marie E  Grundmann, Ursula  Fischer, André  Göbel, Ulf B  Heimesaat, Markus M 
Citation: Bereswill S, etal., PLoS One. 2016 Jun 20;11(6):e0158020. doi: 10.1371/journal.pone.0158020. eCollection 2016.
RGD ID: 39457954
Pubmed: PMID:27322540   (View Abstract at PubMed)
PMCID: PMC4913948   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0158020   (Journal Full-text)


BACKGROUND: Human Campylobacter jejuni infections are progressively rising worldwide. Information about the molecular mechanisms underlying campylobacteriosis, however, are limited. In the present study we investigated whether cytokines such as IL-23, IL-22 and IL-18, which share pivotal functions in host immunity, were involved in mediating intestinal and systemic immunopathological responses upon C. jejuni infection.
METHODOLOGY/PRINCIPAL FINDINGS: To assure stable infection, gnotobiotic (i.e. secondary abiotic) IL-23p19-/-, IL-22-/- and IL-18-/- mice were generated by broad-spectrum antibiotic treatment. Following peroral C. jejuni strain 81-176 infection, mice of all genotypes harbored comparably high pathogenic loads in their intestines. As compared to wildtype controls, however, IL-18-/- mice displayed less distinct C. jejuni induced sequelae as indicated by less pronounced large intestinal shrinkage and lower numbers of apoptotic cells in the colonic epithelial layer at day 8 postinfection (p.i.). Furthermore, lower colonic numbers of adaptive immune cells including regulatory T cells and B lymphocytes were accompanied by less distinct secretion of pro-inflammatory cytokines such as TNF and IFN-γ and lower IL-17A mRNA expression levels in colonic ex vivo biopsies of infected IL-18-/- as compared to wildtype mice. Upon C. jejuni infection, colonic IL-23p19 expression was up-regulated in IL-18-/- mice only, whereas IL-22 mRNA levels were lower in uninfected and infected IL-23p19-/- as well as infected IL-18-/- as compared to respective wildtype control mice. Remarkably, not only intestinal, but also systemic infection-induced immune responses were less pronounced in IL-18-/- mice as indicated by lower TNF, IFN-γ and IL-6 serum levels as compared to wildtype mice.
CONCLUSION/SIGNIFICANCE: We here show for the first time that IL-18 is essentially involved in mediating C. jejuni infection in the gnotobiotic mouse model. Future studies need to further unravel the underlying regulatory mechanisms orchestrating pathogen-host interaction.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL23AHumancampylobacteriosis  ISOIl23a (Mus musculus) RGD 
Il23aRatcampylobacteriosis  ISOIl23a (Mus musculus) RGD 
Il23aMousecampylobacteriosis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il23a  (interleukin 23 subunit alpha)

Genes (Mus musculus)
Il23a  (interleukin 23, alpha subunit p19)

Genes (Homo sapiens)
IL23A  (interleukin 23 subunit alpha)


Additional Information