RGD Reference Report - Gamma interferon and interleukin-1 receptor 1 regulate neutrophil recruitment to the corneal stroma in a murine model of Onchocerca volvulus keratitis. - Rat Genome Database

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Gamma interferon and interleukin-1 receptor 1 regulate neutrophil recruitment to the corneal stroma in a murine model of Onchocerca volvulus keratitis.

Authors: Gentil, K  Pearlman, E 
Citation: Gentil K and Pearlman E, Infect Immun. 2009 Apr;77(4):1606-12. doi: 10.1128/IAI.00671-08. Epub 2009 Jan 21.
RGD ID: 8662882
Pubmed: PMID:19168746   (View Abstract at PubMed)
PMCID: PMC2663151   (View Article at PubMed Central)
DOI: DOI:10.1128/IAI.00671-08   (Journal Full-text)

Toll-like receptor 2 (TLR2) is an essential mediator of corneal inflammation induced by the filarial nematode Onchocerca volvulus, which harbors endosymbiotic Wolbachia bacteria. TLR2 is also required for dendritic cell activation, gamma interferon (IFN-gamma) production, and neutrophil recruitment to the cornea. To examine the role of IFN-gamma in O. volvulus keratitis, C57BL/6 and IFN-gamma(-/-) mice were immunized subcutaneously, and a soluble antigen extract from O. volvulus adult worms (OvAg) was injected into the corneal stroma of each animal. We found that, in the absence of IFN-gamma, neutrophil recruitment to the cornea was significantly impaired, whereas there was no effect on eosinophil infiltration. Since the cornea contains resident macrophages and fibroblasts and our previous studies showed that CXC chemokines mediate neutrophil recruitment, we examined the role of recombinant IFN-gamma (rIFN-gamma) on each cell type. We found no effect of rIFN-gamma on CXC chemokine production by macrophages or corneal fibroblasts, either alone or with filarial extracts; in contrast, rIFN-gamma was found to enhance OvAg-induced tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-1alpha, and IL-1beta in macrophages. Furthermore, we found that rTNF-alpha, rIL-1alpha, or rIL-1beta induced CXC chemokine production by corneal fibroblasts but not by macrophages. To determine the relative contributions of endogenous cytokines, we injected OvAg into the corneal stroma of C57BL/6, IL-1 receptor 1(-/-) (IL-1R1(-/-)), and TNF-alphaR1/2(-/-) mice and examined neutrophil recruitment. We found that neutrophil infiltration was impaired in IL-1R1(-/-) mice but not in TNF-alphaR1/2(-/-) mice. IFN-gamma therefore appears to regulate neutrophil recruitment to the corneal stroma by enhancing TLR2 expression and OvAg-induced IL-1alpha and IL-1beta production by macrophages in the cornea, which then induce IL-1R1-dependent production of CXC chemokine by resident corneal fibroblasts.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1R1HumanOcular Onchocerciasis  ISOIl1r1 (Mus musculus) RGD 
Il1r1RatOcular Onchocerciasis  ISOIl1r1 (Mus musculus) RGD 
Il1r1MouseOcular Onchocerciasis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1r1  (interleukin 1 receptor type 1)

Genes (Mus musculus)
Il1r1  (interleukin 1 receptor, type I)

Genes (Homo sapiens)
IL1R1  (interleukin 1 receptor type 1)


Additional Information