June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Innate Interactions of Bacillus S-Layer During Endophthalmitis
Author Affiliations & Notes
  • Md Huzzatul Mursalin
    University of Oklahoma Health Science Centre, Oklahoma City, Oklahoma, United States
  • Phillip S Coburn
    University of Oklahoma Health Science Centre, Oklahoma City, Oklahoma, United States
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Erin Livingston
    University of Oklahoma Health Science Centre, Oklahoma City, Oklahoma, United States
  • Frederick Christian Miller
    University of Oklahoma Health Science Centre, Oklahoma City, Oklahoma, United States
  • Roger Astley
    University of Oklahoma Health Science Centre, Oklahoma City, Oklahoma, United States
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Ana Flores Mireles
    University of Notre Dame, Notre Dame, Indiana, United States
  • Michelle C. Callegan
    University of Oklahoma Health Science Centre, Oklahoma City, Oklahoma, United States
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Md Huzzatul Mursalin, None; Phillip Coburn, None; Erin Livingston, None; Frederick Miller, None; Roger Astley, None; Ana Mireles, None; Michelle Callegan, None
  • Footnotes
    Support  NIH Grant EY024140, NIH Grant EY025947, NIH Grant EY028066, NIH Grant EY021725, Presbyterian Health Foundation Research Support Grant
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 445. doi:
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    • Get Citation

      Md Huzzatul Mursalin, Phillip S Coburn, Erin Livingston, Frederick Christian Miller, Roger Astley, Ana Flores Mireles, Michelle C. Callegan; Innate Interactions of Bacillus S-Layer During Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):445.

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

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Abstract

Purpose : To explore the mechanisms by which Bacillus S-layer protein (SLP) contributes to intraocular inflammation during endophthalmitis.

Methods : We compared phenotypes of Wild-type (WT) and SLP-deficient (△slpA) Bacillus thuringiensis by analyzing bacterial adherence to and phagocytosis by human retinal Muller cells and phagocytosis by human and mouse neutrophils. Innate immune receptor activation by the Bacillus envelope and purified SLP was analyzed using TLR2 and TLR4 reporter cell lines. A synthetic TLR2/4 inhibitor was used as a control for this receptor activation. To induce endophthalmitis, mice were injected intravitreally with 100 CFU WT or △slpA B. thuringiensis. At 4 hours postinfection, a group of WT-infected mice was treated intravitreally with the TLR2/4 inhibitor. At 10 hours postinfection, infected eyes were analyzed for bacterial counts, histology, inflammation, and retinal function.

Results : B. thuringiensis SLP contributed to adherence to retinal cells, and protected this pathogen from Muller cell- and neutrophil-mediated phagocytosis. The B. thuringiensis envelope activated TLR2 and, surprisingly, TLR4, suggesting the presence of a surface-associated TLR4 agonist in Bacillus. Purified SLP from B. thuringiensis activated TLR4, as well as TLR2, in vitro. Growth of WT B. thuringiensis was significantly greater and caused more inflammation in untreated eyes than in infected eyes treated with the TLR2/4 inhibitor. Retinal function analysis also showed greater retention of A-wave and B-wave function in infected eyes treated with the TLR2/4 inhibitor. The TLR2/4 inhibitor was not antibacterial in vitro and did not cause inflammation when injected into uninfected eyes.

Conclusions : Taken together, these results suggest a potential role for Bacillus SLP in host innate-bacterial interactions, as well as in endophthalmitis pathogenesis via TLR2- and TLR4-mediated pathways. This is also the first study to demonstrate an anti-inflammatory therapeutic effect from targeting TLRs during bacterial endophthalmitis.

This is a 2020 ARVO Annual Meeting abstract.

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