885. Innate immune response in Candida albicans endophthalmitis: the role of Toll-like receptor signaling
Session: Poster Abstract Session: Biomarkers and Adverse Events
Friday, October 9, 2015
Room: Poster Hall
Posters
  • IDSA-2015 Poster.pdf (1.2 MB)
  • Background: Endophthalmitis is a serious complication of ocular trauma and surgery and often leads to blindness and visual disability. It is well established that the Toll-like receptors (TLRs) play an important role in host defense against microbial pathogens; however, relatively little is known about their role in the pathogenesis of fungal endophthalmitis. In this study, we developed a mouse model of Candida albicans endophthalmitis in order to study host-pathogen interactions in this disease.

    Methods: Endophthalmitis was induced in wild type (WT) C57BL/6 and TLR2 KO mice by intravitreal injections of C. albicans. Disease progression was monitored by assessing clinical score, fungal burden, electroretinography (ERG), and retinal tissue damage (H&E staining). Levels of inflammatory cytokines/chemokines were determined using quantitative RT-PCR (qRT-PCR) and ELISA. Flow cytometry was used to assess neutrophil infiltration. TLR2 expression was determined by qRT-PCR and Western blot.

    Results: Our dose-response study revealed that 6,500 CFU of C. albicans caused endophthalmitis in WT mice, as evidenced by increased levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and chemokines (KC and MIP-2) in infected eyes. The time-course studies showed increased fungal burden at 24 and 48 hours post-infection, followed by a decrease at 72 and 96 hours. This coincided with increased PMN infiltration, and retinal tissue damage. Retinal function was reduced in a time-dependent manner, as determined by ERG analysis. qRT-PCR and Western blot analysis of infected eyes showed increased expression of TLR2. A deficiency of TLR2 (TLR2 KO mice) rendered the mice with increased susceptibility towards C. albicans endophthalmitis.

    Conclusion: These results indicate that the retina/retinal cells possess the ability to recognize and respond to the fungal pathogens and that TLR2-signaling mediates innate responses to C. albicans.

    Ashok Kumar, Ph.D.1, Bruce Rottmann, BS1, Sanjay Revankar, MD2 and Pranatharthi Chandrasekar, MD, FIDSA3, (1)Ophthalmology, Wayne State University, Detroit, MI, (2)Infectious Diseases, Detroit Medical Center / Wayne State University, Detroit, MI, (3)Infectious Diseases, Wayne State University, Detroit, MI

    Disclosures:

    A. Kumar, None

    B. Rottmann, None

    S. Revankar, Astellas: Investigator , Research grant
    Merck: Investigator , Research grant
    Gilead: Investigator , Research grant

    P. Chandrasekar, Astellas: Speaker's Bureau , Speaker honorarium

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.