Role of Toll-Like Receptor (TLR) 2 in Experimental Bacillus cereus Endophthalmitis

Novosad, Billy D.; Astley, Roger; Callegan, Michelle C.

doi:10.1371/journal.pone.0028619

Cited by 40 publications

(82 citation statements)

References 38 publications

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“…Retinal function was analyzed by ERG as previously described (25,28,34). ERG is a technique used to analyze retinal function.…”

Section: And Tlr4mentioning

confidence: 99%

“…As an indicator of retinal function, the A-wave and B-wave amplitudes were measured from the initiation of the light flash to the trough of the A-wave and from the trough of the A-wave to the peak of the B-wave. (25,28,34). Eyes were homogenized with 1-mm sterile glass beads (Biospec Products, Inc., Bartlesville, OK) in phosphatebuffered saline (PBS).…”

Section: And Tlr4mentioning

confidence: 99%

“…PMN influx into the eye was estimated by quantifying myeloperoxidase (MPO) levels in whole-eye homogenates at 0, 4, 8, and 12 h postinfection by a sandwich enzyme-linked immunosorbent assay (ELISA) (mouse MPO ELISA kit; Hycult Biotech, Plymouth Meeting, PA), as previously described (25,28). Homogenates of uninfected eyes served as negative controls.…”

Section: And Tlr4mentioning

confidence: 99%

“…Tolllike receptors (TLRs) initially recognize bacterial components and induce an inflammatory response in an attempt to clear the pathogen. TLRs are important in mounting an ocular inflammatory response to bacteria during keratitis (17)(18)(19)(20), uveitis (21)(22)(23)(24), and endophthalmitis (25)(26)(27). During Bacillus endophthalmitis, TLRmediated bacterial recognition results in proinflammatory mediator synthesis and an influx of polymorphonuclear neutrophils (PMN), which have the potential to cause irreversible bystander damage to interior tissues of the eye.…”

mentioning

confidence: 99%

“…During Bacillus endophthalmitis, TLRmediated bacterial recognition results in proinflammatory mediator synthesis and an influx of polymorphonuclear neutrophils (PMN), which have the potential to cause irreversible bystander damage to interior tissues of the eye. We previously reported the significant contribution of TLR2 (25) and a limited role for TLR5 (28) in the pathogenesis of B. cereus endophthalmitis. However, the presence of residual inflammation in the eyes of TLR2 Ϫ/Ϫ mice infected with B. cereus suggested the involvement of additional innate immune recognition and signaling mechanisms in intraocular inflammation during this disease.…”

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confidence: 99%

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Unexpected Roles for Toll-Like Receptor 4 and TRIF in Intraocular Infection with Gram-Positive Bacteria

et al. 2015

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Inflammation caused by infection with Gram-positive bacteria is typically initiated by interactions with Toll-like receptor 2 (TLR2). Endophthalmitis, an infection and inflammation of the posterior segment of the eye, can lead to vision loss when initiated by a virulent microbial pathogen. Endophthalmitis caused by Bacillus cereus develops as acute inflammation with infiltrating neutrophils, and vision loss is potentially catastrophic. Residual inflammation observed during B. cereus endophthalmitis in TLR2 ؊/؊ mice led us to investigate additional innate pathways that may trigger intraocular inflammation. We first hypothesized that intraocular inflammation during B. cereus endophthalmitis would be controlled by MyD88-and TRIF-mediated signaling, since MyD88 and TRIF are the major adaptor molecules for all bacterial TLRs. In MyD88 ؊/؊ and TRIF ؊/؊ mice, we observed significantly less intraocular inflammation than in eyes from infected C57BL/6J mice, suggesting an important role for these TLR adaptors in B. cereus endophthalmitis. These results led to a second hypothesis, that TLR4, the only TLR that signals through both MyD88 and TRIF signaling pathways, contributed to inflammation during B. cereus endophthalmitis. Surprisingly, B. cereus-infected TLR4 ؊/؊ eyes also had significantly less intraocular inflammation than infected C57BL/6J eyes, indicating an important role for TLR4 in B. cereus endophthalmitis. Taken together, our results suggest that TLR4, TRIF, and MyD88 are important components of the intraocular inflammatory response observed in experimental B. cereus endophthalmitis, identifying a novel innate immune interaction for B. cereus and for this disease. Bacillus cereus is a Gram-positive, spore-forming, and beta-hemolytic soil bacterium (1). Commonly identified as a causative agent of foodborne illnesses, B. cereus is also associated with a multitude of clinical conditions, such as central nervous system infections (2), pneumonia (3), endocarditis (4), and gas-gangrene-like cutaneous infections (5). B. cereus also causes a virulent form of endophthalmitis, an intraocular inflammatory condition resulting from the introduction of microorganisms into the posterior segment of the eye following surgery or injury or from a distant site of infection. This infection causes irreversible damage to the retina, often leading to vision loss within 1 or 2 days (6). Typically, B. cereus endophthalmitis occurs following a penetrating eye injury (posttraumatic) with retained intraocular foreign bodies (7, 8) but has also been reported in postoperative patients (9-11). Fewer than 30% of posttraumatic B. cereus endophthalmitis patients retained useful vision, and out of these, only 9% retained 20/70 vision or better (7, 12). Moreover, 48% of B. cereus and other Bacillus species infections required evisceration or enucleation of the eye despite therapeutic intervention (7, 12). Intraocular inflammation that occurs during B. cereus endophthalmitis interferes with the clarity of the visual axis, contributing to disruption...

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“…Retinal function was analyzed by ERG as previously described (25,28,34). ERG is a technique used to analyze retinal function.…”

Section: And Tlr4mentioning

confidence: 99%

Section: And Tlr4mentioning

confidence: 99%

Section: And Tlr4mentioning

confidence: 99%