| Role of defensins in corneal epithelial barrier function against Pseudomonas aeruginosa traversal. | |
| | |
MedLine Citation:
|
PMID: 21115716 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Studies have shown that epithelium-expressed antimicrobial peptides (AMPs), e.g., β-defensins, play a role in clearing bacteria from mouse corneas already infected with Pseudomonas aeruginosa. Less is known about the role of AMPs in allowing the cornea to resist infection when healthy. We previously reported that contact lens exposure, a major cause of P. aeruginosa keratitis, can inhibit the upregulation of human β-defensin 2 (hBD-2) by corneal epithelial cells in response to P. aeruginosa antigens in vitro. Here, we studied the role of AMPs in maintaining the corneal epithelial barrier to P. aeruginosa penetration using both in vitro (human) and in vivo (mouse) experiments. Results showed that preexposing human corneal epithelial multilayers to bacterial antigens in a culture supernatant (known to upregulate AMP expression) reduced epithelial susceptibility to P. aeruginosa traversal up to 6-fold (P < 0.001). Accordingly, small interfering RNA (siRNA) knockdown of any one of four AMPs expressed by human epithelia promoted P. aeruginosa traversal by more than 3-fold (P < 0.001). The combination knockdown of AMPs further enhanced susceptibility to bacterial traversal by ∼8-fold (P < 0.001). In vivo experiments showed that the loss of murine β-defensin 3 (mBD-3), a murine ortholog of hBD-2, enhanced corneal susceptibility to P. aeruginosa. The uninjured ocular surface of mBD-3(-/-) mice showed a reduced capacity to clear P. aeruginosa, and their corneal epithelia were more susceptible to bacterial colonization, even when inoculated ex vivo to exclude tear fluid effects. Together, these in vitro and in vivo data show functional roles for AMPs in normal corneal epithelial cell barrier function against P. aeruginosa. |
| | |
Authors:
|
Danielle K Augustin; Susan R Heimer; Connie Tam; Wing Y Li; Jeff M Le Due; David J Evans; Suzanne M J Fleiszig |
Related Documents
:
|
6359986 - In vitro response of murine alveolar and peritoneal macrophages to mycobacterium intrac... 3393096 - Biological activities of lipid a from vibrio parahaemolyticus: stimulation of murine pe... 11045296 - Cd40 ligand expression on macrophages during peritonitis in continuous ambulatory perit... 4085676 - Non-immune non-activated chicken macrophages destroy murine fibroblasts. 9028936 - Interleukin-10 inhibits spontaneous colony-forming unit-granulocyte-macrophage growth f... 17695546 - Ethyl 2- [n-m-chlorobenzyl- (2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-29 |
Journal Detail:
|
Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-01-24 Completed Date: 2011-03-15 Revised Date: 2011-08-03 |
Medline Journal Info:
|
Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
|
Languages: eng Pagination: 595-605 Citation Subset: IM |
Affiliation:
|
Graduate Group in Microbiology, Department of Plant and Microbial Biology, University of California, Berkeley, California, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Line Defensins / metabolism* Epithelium, Corneal / metabolism*, microbiology* Gene Expression Regulation / physiology Humans Mice Mice, Inbred C57BL Mice, Knockout Pseudomonas aeruginosa / physiology* beta-Defensins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
EY011221/EY/NEI NIH HHS; EY019456/EY/NEI NIH HHS; R01 EY011221-14/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Defensins; 0/beta-Defensins; 0/beta-defensin 3, mouse |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ecological basis of the interaction between Pseudozyma flocculosa and powdery mildew fungi.
Next Document: Comparative kinetics of Escherichia coli- and Staphylococcus aureus-specific activation of key immun...