TY - JOUR
T1 - Expression of innate and adaptive immune mediators in human corneal tissue infected with Aspergillus or Fusarium
AU - Karthikeyan, Rajapandian Sivaganesa
AU - Leal, Sixto M.
AU - Prajna, Namperumalsamy Venkatesh
AU - Dharmalingam, Kuppamuthu
AU - Geiser, David M.
AU - Pearlman, Eric
AU - Lalitha, Prajna
N1 - Funding Information:
This work was supported by the Indian Council of Medical Research (grant to P. L.); Alcon Laboratories (grant to P. L.); the Alcon Research Institute (award to E. P.); the National Eye Institute, National Institutes of Health (grants RO1 EY018612 and P30 EY011373 to E. P. and grant F31 EY019841 to S. M. L.); the Research to Prevent Blindness Foundation; and the Ohio Lions Eye Research Foundation.
Funding Information:
The protocol for obtaining corneal ulcer scrapings and post-transplant infected corneas removed at the time of surgery was reviewed and approved by the ethics committee of the Aravind Medical Research Foundation. The research aims and methodology are thoroughly explained to the patients, and the samples are collected after obtaining informed consent. Patients with acute or chronic systemic illness or with any form of immunosuppression or topical steroid therapy were excluded from this study. All studies on patient material were performed in India.
PY - 2011/9/15
Y1 - 2011/9/15
N2 - Background. Filamentous fungi of the genera Aspergillus and Fusarium are major causes of corneal ulcers in the United States and in the developing world and result in significant visual impairment and blindness. Methods. RNA was extracted from 110 patients with corneal ulcers in southern India within 1 week of infection with either Fusarium solani or Aspergillus flavus, and gene expression was determined by quantitative polymerase chain reaction. Posttransplant corneas from later stage disease (>2 weeks after infection) were also examined. Results. Expression of Dectin-1, Toll-like receptor 2 (TLR2), TLR4, TLR9, and NOD-like receptor protein (NLRP)3 messenger RNA was elevated >1000-fold compared with uninfected donor corneas, whereas Dectin-2 was constitutively expressed in uninfected corneas. Furthermore, interleukin 1β (IL-1β) expression was elevated >1000-fold, whereas IL-1α expression was not increased. Expression of IL-8, IL-17, and tumor necrosis factor α was also elevated. CD3+ and CD4+ T cells were detected in infected posttransplant corneas. Expression of IL-17 and interferon γ was elevated but not that of IL-4. There were no significant differences in the host response between Aspergillus- and Fusarium-infected corneas at any time point. Conclusions. There is a common innate and adaptive immune response to these filamentous fungi, which includes the generation of T-helper 1 and T-helper 17 cells.
AB - Background. Filamentous fungi of the genera Aspergillus and Fusarium are major causes of corneal ulcers in the United States and in the developing world and result in significant visual impairment and blindness. Methods. RNA was extracted from 110 patients with corneal ulcers in southern India within 1 week of infection with either Fusarium solani or Aspergillus flavus, and gene expression was determined by quantitative polymerase chain reaction. Posttransplant corneas from later stage disease (>2 weeks after infection) were also examined. Results. Expression of Dectin-1, Toll-like receptor 2 (TLR2), TLR4, TLR9, and NOD-like receptor protein (NLRP)3 messenger RNA was elevated >1000-fold compared with uninfected donor corneas, whereas Dectin-2 was constitutively expressed in uninfected corneas. Furthermore, interleukin 1β (IL-1β) expression was elevated >1000-fold, whereas IL-1α expression was not increased. Expression of IL-8, IL-17, and tumor necrosis factor α was also elevated. CD3+ and CD4+ T cells were detected in infected posttransplant corneas. Expression of IL-17 and interferon γ was elevated but not that of IL-4. There were no significant differences in the host response between Aspergillus- and Fusarium-infected corneas at any time point. Conclusions. There is a common innate and adaptive immune response to these filamentous fungi, which includes the generation of T-helper 1 and T-helper 17 cells.
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U2 - 10.1093/infdis/jir426
DO - 10.1093/infdis/jir426
M3 - Article
C2 - 21828275
AN - SCOPUS:80052220145
SN - 0022-1899
VL - 204
SP - 942
EP - 950
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -