Expression of toll-like receptor 4 and its associated lipopolysaccharide receptor complex by resident antigen-presenting cells in the human uvea.
OBJECTIVE
To investigate the in vivo expression of toll-like receptor 4 (TLR4) and its associated lipopolysaccharide (LPS) receptor complex in the human eye.


METHODS
Normal human ocular tissues were evaluated for in vivo TLR4, MD-2, and CD14 mRNA and protein expression by RT-PCR and immunohistochemistry, respectively. The distribution patterns and phenotypes of the cells expressing these proteins were further characterized by confocal microscopy and double-label immunofluorescence studies.


RESULTS
Normal human uvea, retina, sclera, and conjunctiva constitutively expressed TLR4, MD-2, and CD14 mRNA. The protein expression of these molecules was restricted, however, to resident antigen-presenting cells (APCs) in the normal human uvea, consisting mainly of HLA-DR(+) dendritic cells (DCs). These APCs endowed with the complete LPS receptor complex appeared to be strategically positioned in perivascular and subepithelial locations for surveying blood-borne or intraocular LPS. In contrast, other cell types of the normal human cornea, conjunctiva, retina, and sclera did not express TLR4/MD-2 protein in vivo as detectable by immunohistochemistry.


CONCLUSIONS
The present study demonstrates for the first time that resident APCs in the normal human uvea express TLR4 and its associated LPS receptor complex. This has significant implications for the understanding of normal ocular immunity as well as unraveling the potential role of Gram-negative bacteria in the pathogenesis of acute anterior uveitis (AAU).
Chang
John H
JH
Laboratory of Ocular Immunology, Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia.
McCluskey
Peter
P
Wakefield
Denis
D
D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism; D051218:Lymphocyte Antigen 96; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014602:Uvea / Q000378:metabolism*
D000954:Antigens, Surface; D006684:HLA-DR Antigens; C495377:LY96 protein, human; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors