September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Fungal components trigger induction of EAU through a Card9-dependent mechanism
Author Affiliations & Notes
  • Brieanna Brown
    VA Portland Health Care System , Portland, Oregon, United States
  • Ellen J Lee
    VA Portland Health Care System , Portland, Oregon, United States
    Molecular Microbiology & Immunology, Oregon Health & Science University , Portland, Oregon, United States
  • Paige Snow
    VA Portland Health Care System , Portland, Oregon, United States
  • Emily Vance
    VA Portland Health Care System , Portland, Oregon, United States
    Molecular Microbiology & Immunology, Oregon Health & Science University , Portland, Oregon, United States
  • Rachel R Caspi
    Laboratory of Immunology, NEI, NIH, Bethesda, Maryland, United States
  • Holly Lallman Rosenzweig
    VA Portland Health Care System , Portland, Oregon, United States
    Molecular Microbiology & Immunology, Oregon Health & Science University , Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Brieanna Brown, None; Ellen Lee, None; Paige Snow, None; Emily Vance, None; Rachel Caspi, None; Holly Rosenzweig, None
  • Footnotes
    Support  NIH/NEI (grant EY019020), the Department of Veterans Affairs Biomedical Laboratory, and NEI intramural support (project # EY000184)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 502. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Brieanna Brown, Ellen J Lee, Paige Snow, Emily Vance, Rachel R Caspi, Holly Lallman Rosenzweig; Fungal components trigger induction of EAU through a Card9-dependent mechanism. Invest. Ophthalmol. Vis. Sci. 2016;57(12):502.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : The signals that initiate autoreactive T cells to target the eye, which may be of infectious or non-infectious origin, are poorly understood. Our recent work identified Card9, a signaling molecule essential in defense against fungi, as an important determinant in susceptibility to uveitis. Here, we further investigated the ability of fungal triggers, which are commonly encountered in our environment, to induce uveitis and the role of Card9 in pathogenesis of experimental autoimmune uveitis (EAU).

Methods : EAU was induced in wild-type mice (WT, C57BL/6J strain) by immunization with interphotoreceptor retinoid-binding protein (IRBP) and the adjuvant CFA. Uveitis was evaluated with fundus imaging and histology. Adjuvant replacement studies were performed in which CFA was replaced with various mycobacterial cell wall components including trehalose-6,6-dibehenate (TDB, synthetic analog of mycobacterial cord factor), peptidoglycan (PGN), and muramyl dipeptide (MDP), or with heat-killed Candida albicans (HKCA) or its components curdlan, zymosan, or α-mannan. Negative controls using incomplete Freund’s adjuvant (IFA) were also included. To assess the contribution of Card9 in HKCA-induced EAU, uveitis was evaluated in mice sufficient or deficient in Card9.

Results : EAU induced by whole HKCA resulted in robust uveitis that was comparable in severity and onset to EAU induced using CFA (n=10 mice/group). Subsequent adjuvant replacement studies with the fungal cell wall components curdlan, zymosan or α-mannan reproduced the phenotype of EAU with HKCA, while those with mycobacterial components (PGN and MDP) did not (n=8 mice/group). TDB however, did induce the full EAU phenotype and this was dependent on Card9. We found that HKCA-induced EAU was also significantly abrogated by Card9-deficiency (p<0.05; n=10 mice/group) as determined by both fundus imaging and histology.

Conclusions : These experiments serve as a proof-of-principle study to demonstrate the importance of the Card9-signaling pathway in orchestration of autoimmunity targeted to the eye, which can be initiated by either mycobacterial TDB or fungal triggers. Additional studies to elucidate the upstream innate immune receptors that respond to fungal triggers and that activate Card9 (e.g. C-type lectin receptors Dectin-1, Dectin-2, Mincle) are necessary to fully understand the role of fungal triggers in EAU.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×