Abstract |
We previously showed that topical flagellin induces profound mucosal innate protection in the cornea against microbial infection, a response involving multiple genes and cell types. In this study, we used a Candida albicans (CA)-C57BL/6 mouse keratitis model to delineate the contribution of CXCL10- and CXCR3-expressing cells in flagellin-induced protection. Flagellin pretreatment markedly enhanced CXCL10 expression at 6 h post CA infection (hpi), but significantly dampened CXCL10 expression at 24 hpi. At the cellular level, CXCL10 was expressed in the epithelia at 6 hpi in flagellin-pretreated corneas, and concentrated at lesion sites 24 hpi. CXCR3-expressing cells were detected in great numbers at 24 hpi, organized within clusters at the lesion sites in CA-infected corneas. CXCL10 or CXCR3 neutralization increased keratitis severity and dampened flagellin-induced protection. CXCR3-positive cells were identified as NK cells, the depletion of which resulted in severe CA keratitis. Contributions from NK T-cells were excluded by finding no change in flagellin-induced protection in Rag1 KO mice. Recombinant CXCL10 inhibited CA growth in vitro and accelerated fungal clearance and inflammation resolution in vivo. Taken together, our data indicate that epithelium-expressed CXCL10 plays a critical role in fungal clearance and that CXCR3-expressing NK cells contribute to CA eradication in mouse corneas.
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Authors | Xiaowei Liu, Nan Gao, Chen Dong, Li Zhou, Qing-Sheng Mi, Theodore J Standiford, Fu-Shin X Yu |
Journal | European journal of immunology
(Eur J Immunol)
Vol. 44
Issue 9
Pg. 2667-79
(Sep 2014)
ISSN: 1521-4141 [Electronic] Germany |
PMID | 24965580
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Chemical References |
- Chemokine CXCL10
- Cxcl10 protein, mouse
- Cxcr3 protein, mouse
- Homeodomain Proteins
- Receptors, CXCR3
- Flagellin
- RAG-1 protein
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Topics |
- Animals
- Candida albicans
(immunology)
- Candidiasis
(genetics, immunology, therapy)
- Chemokine CXCL10
(genetics, immunology)
- Cornea
(immunology, microbiology, pathology)
- Flagellin
(chemistry, immunology, isolation & purification, pharmacology)
- Gene Expression Regulation
(drug effects, genetics, immunology)
- Homeodomain Proteins
(genetics, immunology)
- Immunity, Cellular
- Immunity, Mucosal
(drug effects, genetics, immunology)
- Keratitis
(genetics, immunology, microbiology, pathology, therapy)
- Killer Cells, Natural
(immunology, pathology)
- Mice
- Mice, Knockout
- Pseudomonas aeruginosa
(chemistry)
- Receptors, CXCR3
(genetics, immunology)
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