Spontaneous bacterial keratitis in CD36 knockout mice.
OBJECTIVE
CD36 is a Class B scavenger receptor that is constitutively expressed in the corneal epithelium and has been implicated in many homeostatic functions, including the homeostasis of the epidermal barrier. The aim of this study is to determine (1) whether CD36 is required for the maintenance of the corneal epithelial barrier to infection, and (2) whether CD36-deficient mice present with an increased susceptibility to bacterial keratitis.


METHODS
The corneas of CD36(-/-), TSP1(-/-), TLR2(-/-), and C57BL/6 WT mice were screened via slit lamp microscopy or ex vivo analysis. The epithelial tight junctions and mucin layer were assessed via LC-biotin and Rose Bengal staining, respectively. Bacterial quantification was performed on corneal buttons and GFP-expressing Staphylococcus aureus was used to study bacterial binding.


RESULTS
CD36(-/-) mice develop spontaneous corneal defects that increased in frequency and severity with age. The mild corneal defects were characterized by a disruption in epithelial tight junctions and the mucin layer, an infiltrate of macrophages, and increased bacterial binding. Bacterial quantification revealed high levels of Staphylococcus xylosus in the corneas of CD36(-/-) mice with severe defects, but not in wild-type controls.


CONCLUSIONS
CD36(-/-) mice develop spontaneous bacterial keratitis independent of TLR2 and TSP1. The authors conclude that CD36 is a critical component of the corneal epithelial barrier, and in the absence of CD36 the barrier breaks down, allowing bacteria to bind to the corneal epithelium and resulting in spontaneous keratitis. This is the first report of spontaneous bacterial keratitis in mice.
Klocke
Julia
J
Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Barcia
Rita N
RN
Heimer
Susan
S
Cario
Elke
E
Zieske
James
J
Gilmore
Michael S
MS
Ksander
Bruce R
BR
Gregory
Meredith S
MS
D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D003320:Corneal Ulcer / Q000382:microbiology* / Q000473:pathology; D019573:Epithelium, Corneal / Q000378:metabolism; D015818:Eye Infections, Bacterial / Q000382:microbiology* / Q000473:pathology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity; D019700:Thrombospondin 1 / Q000502:physiology; D019108:Tight Junctions / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000502:physiology
D018955:CD36 Antigens; D009077:Mucins; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D019700:Thrombospondin 1; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D049452:Green Fluorescent Proteins