PMID- 25678692
OWN - NLM
STAT- MEDLINE
DCOM- 20150903
LR  - 20221207
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 56
IP  - 3
DP  - 2015 Feb 12
TI  - In Vivo Role of TLR2 and MyD88 Signaling in Eliciting Innate Immune Responses in 
      Staphylococcal Endophthalmitis.
PG  - 1719-32
LID - 10.1167/iovs.14-16087 [doi]
AB  - PURPOSE: The purpose of this study was to investigate the protective mechanisms 
      evoked by TLR2 and MyD88 signaling in bacterial endophthalmitis in vivo. METHODS: 
      Endophthalmitis was induced in wild-type (WT), TLR2(-/-), MyD88(-/-), and 
      Cnlp(-/-) mice by intravitreal injections of a laboratory strain (RN6390) and two 
      endophthalmitis isolates of Staphylococcus aureus. Disease progression was 
      monitored by assessing corneal and vitreous haze, bacterial burden, and retinal 
      tissue damage. Levels of inflammatory cytokines/chemokines were determined using 
      quantitative RT-PCR (qRT-PCR) and ELISA. Flow cytometry was used to assess 
      neutrophil infiltration. Cathelicidin-related antimicrobial peptide (CRAMP) 
      expression was determined by immunostaining and dot blot. RESULTS: Eyes infected 
      with either laboratory or clinical isolates exhibited higher levels of 
      inflammatory mediators at the early stages of infection (</=24 hours) in WT mice 
      than in TLR2(-/-) or MyD88(-/-) mice. However, their levels surpassed that of WT 
      mice at the later stages of infection (>48 hours), coinciding with increased 
      bacterial burden and retinal damage. Both TLR2(-/-) and MyD88(-/-) retinas 
      produced reduced levels of CRAMP, and its deficiency (Cnlp(-/-)) rendered the 
      mice susceptible to increased bacterial burden and retinal tissue damage as early 
      as 1 day post infection. Analyses of inflammatory mediators and neutrophil levels 
      in WT versus Cnlp(-/-) mice showed a trend similar to that observed in TLR2 and 
      MyD88 KO mice. Furthermore, we observed that even a 10-fold lower infective dose 
      of S. aureus was sufficient to cause endophthalmitis in TLR2(-/-) and MyD88(-/-) 
      mice. CONCLUSIONS: TLR2 and MyD88 signaling plays an important role in protecting 
      the retina from staphylococcal endophthalmitis by production of the antimicrobial 
      peptide CRAMP.
CI  - Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
FAU - Talreja, Deepa
AU  - Talreja D
AD  - Department of Ophthalmology/Kresge Eye Institute, Wayne State University, 
      Detroit, Michigan, United States Department of Biological Sciences, Oakland 
      University, Rochester, Michigan, United States.
FAU - Singh, Pawan Kumar
AU  - Singh PK
AD  - Department of Ophthalmology/Kresge Eye Institute, Wayne State University, 
      Detroit, Michigan, United States Department of Anatomy and Cell Biology, Wayne 
      State University, Detroit, Michigan, United States.
FAU - Kumar, Ashok
AU  - Kumar A
AD  - Department of Ophthalmology/Kresge Eye Institute, Wayne State University, 
      Detroit, Michigan, United States.
LA  - eng
GR  - P30 EY004068/EY/NEI NIH HHS/United States
GR  - R01 EY019888/EY/NEI NIH HHS/United States
GR  - EY19888/EY/NEI NIH HHS/United States
GR  - P30EY004068/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150212
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Cathelicidins)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides
MH  - Cathelicidins/metabolism
MH  - Chemokines/metabolism
MH  - Cytokines/metabolism
MH  - Endophthalmitis/*genetics/*immunology/pathology
MH  - Immunity, Innate/*genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/*genetics
MH  - Retina/immunology/pathology
MH  - Signal Transduction/*genetics
MH  - Staphylococcal Infections/*genetics/*immunology/pathology
MH  - Toll-Like Receptor 2/*genetics
PMC - PMC4356198
OTO - NOTNLM
OT  - CRAMP
OT  - MyD88
OT  - Staphylococcus aureus
OT  - TLR2
OT  - endophthalmitis
OT  - inflammation
OT  - retinal damage
EDAT- 2015/02/14 06:00
MHDA- 2015/09/04 06:00
PMCR- 2015/09/01
CRDT- 2015/02/14 06:00
PHST- 2015/02/14 06:00 [entrez]
PHST- 2015/02/14 06:00 [pubmed]
PHST- 2015/09/04 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - iovs.14-16087 [pii]
AID - IOVS-14-16087 [pii]
AID - 10.1167/iovs.14-16087 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2015 Feb 12;56(3):1719-32. doi: 10.1167/iovs.14-16087.