Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

Kochan, Travis J.; Singla, Anuj; Tosi, Joaquin; Kumar, Ashok

doi:10.1128/iai.00149-12

Cited by 75 publications

(91 citation statements)

References 62 publications

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“…TLR2 is also important in mediating inflammation in Staphylococcus aureus endophthalmitis (Kochan et al, 2012 and Talreja et al, 2015). We do not know whether the pili of Bacillus interact with these innate immune receptors and are, in fact, TLR ligands.…”

Section: Discussionmentioning

confidence: 99%

The role of pili in Bacillus cereus intraocular infection

Callegan

Parkunan

Randall

et al. 2017

Experimental Eye Research

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Bacterial endophthalmitis is a potentially blinding intraocular infection. The bacterium Bacillus cereus causes a devastating form of this disease which progresses rapidly, resulting in significant inflammation and loss of vision within a few days. The outer surface of B. cereus incites the intraocular inflammatory response, likely through interactions with innate immune receptors such as TLRs. This study analyzed the role of B. cereus pili, adhesion appendages located on the bacterial surface, in experimental endophthalmitis. To test the hypothesis that the presence of pili contributed to intraocular inflammation and virulence, we analyzed the progress of experimental endophthalmitis in mouse eyes infected with wild type B. cereus (ATCC 14579) or its isogenic pilus-deficient mutant (ΔbcpA-srtD-bcpB or ΔPil). One hundred CFU were injected into the mid-vitreous of one eye of each mouse. Infections were analyzed by quantifying intraocular bacilli and retinal function loss, and by histology from 0 to 12 h postinfection. In vitro growth and hemolytic phenotypes of the infecting strains were also compared. There was no difference in hemolytic activity (1:8 titer), motility, or in vitro growth (p>0.05, every 2 h, 0-18 h) between wild type B. cereus and the ΔPil mutant. However, infected eyes contained greater numbers of wild type B. cereus than ΔPil during the infection course (p≤0.05, 3-12 h). Eyes infected with wild type B. cereus experienced greater losses in retinal function than eyes infected with the ΔPil mutant, but the differences were not always significant. Eyes infected with ΔPil or wild type B. cereus achieved similar degrees of severe inflammation. The results indicated that the intraocular growth of pilus-deficient B. cereus may have been better controlled, leading to a trend of greater retinal function in eyes infected with the pilus-deficient strain. Although this difference was not enough to significantly alter the severity of the inflammatory response, these results suggest a potential role for pili in protecting B. cereus from clearance during the early stages of endophthalmitis, which is a newly described virulence mechanism for this organism and this infection.

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Section: Discussionmentioning

confidence: 99%

The role of pili in Bacillus cereus intraocular infection

Callegan

Parkunan

Randall

et al. 2017

Experimental Eye Research

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“…As ZIKV was found to infect multiple retinal cell types and to induce the expression of multiple potential entry receptors, we next determined whether ZIKVinfected retinal cells elicit an innate immune response. TLRs have been shown to play an important role in orchestrating retinal innate responses in microbial infection (30,31,(38)(39)(40)(41), with TLR3 being implicated in viral infection. Our data showed that TLR3 mRNA expression was significantly upregulated in both ZIKVinfected Pr.…”

Section: Zikv Infects Multiple Retinal Cell Types and Induces Cell Dementioning

confidence: 99%

Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes

et al. 2017

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“…The effect of Ply187 treatment on intraocular inflammation was assessed by measuring cytokine/chemokine levels in retinal tissue lysates via an enzymelinked immunosorbent assay (ELISA) for mouse interleukin-6 (IL-6), IL-1␤, and tumor necrosis factor alpha (TNF-␣) (BD Biosciences, San Diego, CA) and macrophage inflammatory protein 2 (MIP-2) and KC (R&D Systems, Minneapolis, MN). Flow cytometry with an Accuri C6 apparatus (BD Biosciences, Ann Arbor, MI) was used to determine polymorphonuclear leukocyte (PMN) infiltration as described previously (31,32).…”

Section: Bacterial Burden Estimations the Bacterial Burdens In Both mentioning

confidence: 99%

Intravitreal Injection of the Chimeric Phage Endolysin Ply187 Protects Mice from Staphylococcus aureus Endophthalmitis

Singh

Donovan

Kumar

2014

Antimicrob Agents Chemother

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cThe treatment of endophthalmitis is becoming very challenging due to the emergence of multidrug-resistant bacteria. Hence, the development of novel therapeutic alternatives for ocular use is essential. Here, we evaluated the therapeutic potential of Ply187AN-KSH3b, a chimeric phage endolysin derived from the Ply187 prophage, in a mouse model of Staphylococcus aureus endophthalmitis. Our data showed that the chimeric Ply187 endolysin exhibited strong antimicrobial activity against both methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA) strains, as evidenced by MIC determinations, reductions in turbidity, and disruption of biofilms. Moreover, exposure of S. aureus to Ply187 for up to 10 generations did not lead to resistance development. The intravitreal injection of chimeric Ply187 (at 6 or 12 h postinfection) significantly improved the outcome of endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinogram analysis. Furthermore, phage lysin treatment significantly reduced the bacterial burden and the levels of inflammatory cytokines and neutrophil infiltration in the eyes. These results indicate that the intravitreal administration of a phage lytic enzyme attenuates the development of bacterial endophthalmitis in mice. To the best of our knowledge, this is the first study demonstrating the therapeutic use of phage-based antimicrobials in ocular infections.

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Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

Cited by 75 publications

References 62 publications

The role of pili in Bacillus cereus intraocular infection

The role of pili in Bacillus cereus intraocular infection

Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes

Intravitreal Injection of the Chimeric Phage Endolysin Ply187 Protects Mice from Staphylococcus aureus Endophthalmitis

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