PMID- 22665968
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 18
DP  - 2012
TI  - Strain-dependent production of interleukin-17/interferon-gamma and matrix 
      remodeling-associated genes in experimental Candida albicans keratitis.
PG  - 1215-25
AB  - PURPOSE: The aim of this study was to investigate the role of genetic background 
      in determining the development or prognosis of experimental fungal keratitis by 
      comparing the disease courses and related molecules of experimental Candida 
      albicans in two common mouse strains. METHODS: After intrastromal inoculation of 
      1 x 10(5)C. albicans blastospores into corneas of Balb/c and C57BL/6 mice, all 
      mice developed typical keratitis. The disease was monitored using a slit lamp 
      microscope and scored for comparison of symptoms. At desired time points, blood 
      was collected and corneal homogenates were prepared for enzyme-linked 
      immunosorbent assay measurement of interferon (IFN)gamma or interleukin (IL)17. Other 
      corneas were processed for histological evaluation, pathogen load measurement, or 
      total RNA extraction, the last of which was subjected to reverse transcription in 
      conjunction with real-time PCR to measure genes of interest in terms of 
      collagens, matrix metalloproteinases (MMPs), and the tissue inhibitors of MMPs 
      (TIMPs). RESULTS: The infected corneas from the two strains presented different 
      manifestations. Corneal transparency was less affected in Balb/c mice than in 
      C57BL/6 mice, and Balb/c corneas contained fewer pathogens than C57BL/6 corneas 
      during the measured period (10 days). In both strains, keratitis started to 
      resolve around days 7-10, but C57BL/6 mice healed slower than Balb/c mice as 
      indicated by disease presentation, histology, and pathogen burden assay. By day 7 
      post infection, pseudohyphae were rare but cellular infiltration remained 
      intensive in both strains. The surface of the Balb/c corneas remained relatively 
      intact and smooth, and C57BL/6 corneal lesions produced open erosion areas. 
      Perforation was never seen in the current study setting. In both sera and 
      corneas, IL17 expression increased earlier than IFNgamma, and C57BL/6 mice produced 
      higher IL17 levels and lower IFNgamma levels than Balb/c mice. Compared with C57BL/6 
      mice, Balb/c corneas produced more MMP-2, Col3a1, and Col4a1, and less or 
      equivalent TIMP-2 at all detected time points. They also produced more MMP-13, 
      less MMP-8, MMP-9, and TIMP-1 at day 3 post infection, but less MMP-13, basically 
      equivalent MMP-8, and more MMP-9 at later time points. CONCLUSIONS: The disease 
      course of experimental C. albicans keratitis depends on the genetic background of 
      the host animals. The balance between IL17 and IFNgamma, as well as among the common 
      injury- and wound healing-related proteins, may contribute to the pathogenesis of 
      C. albicans keratitis. This study suggests that great variance of disease 
      presentation should be expected for human subjects with Candida keratitis.
FAU - Zou, Yanli
AU  - Zou Y
AD  - Department of Immunology, Taishan Medical University, Taishan, China.
FAU - Zhang, Hongbo
AU  - Zhang H
FAU - Li, Hongxia
AU  - Li H
FAU - Chen, Hao
AU  - Chen H
FAU - Song, Wengang
AU  - Song W
FAU - Wang, Yiqiang
AU  - Wang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120510
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Interleukin-17)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.- (Metalloproteases)
SB  - IM
MH  - Animals
MH  - Candida albicans/immunology/pathogenicity
MH  - Collagen/*genetics/immunology
MH  - Cornea/*immunology/microbiology
MH  - Genetic Variation
MH  - Host Specificity
MH  - Interferon-gamma/*biosynthesis/immunology
MH  - Interleukin-17/*biosynthesis/immunology
MH  - Keratitis/*immunology/microbiology
MH  - Male
MH  - Metalloproteases/*genetics/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Tissue Inhibitor of Metalloproteinases/genetics/immunology
PMC - PMC3365135
EDAT- 2012/06/06 06:00
MHDA- 2012/12/14 06:00
PMCR- 2012/01/01
CRDT- 2012/06/06 06:00
PHST- 2012/02/13 00:00 [received]
PHST- 2012/05/06 00:00 [accepted]
PHST- 2012/06/06 06:00 [entrez]
PHST- 2012/06/06 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - 127 [pii]
AID - 2012MOLVIS0074 [pii]
PST - ppublish
SO  - Mol Vis. 2012;18:1215-25. Epub 2012 May 10.