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Changjun Wang, Fang Bian, Yangyan Xiao, Simmons Ken T, Mahira Zaheer, Stephen C Pflugfelder, Cintia S De Paiva; Commensal Bacteria Modulate Ocular Surface Inflammatory Response to Liposaccharide. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3916.
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© ARVO (1962-2015); The Authors (2016-present)
There is growing evidence that commensal bacteria can modulate inflammatory responses at distant sites. This study evaluated the ocular surface response to topically applied TLR4 ligand in mice with and without commensal bacteria.
Conventionally housed (CON) C57BL/6 female mice were compared to mice that received oral antibiotics (ABX) for 14 days. A single dose of lipopolysaccharide (LPS) or vehicle (endotoxin-free water) was applied to the cornea. Corneal epithelium and conjunctiva were extracted after 4 hours to analyze expression of innate and adaptive immune mediators (IL-1β, IL-6, TNF-a, CXCL10, IL-12, and IFN-g) by PCR and expression of dendritic cell (CD11b, CD11c) and their activation markers (MHC II and CD86) was evaluated in draining nodes. A separate group of germ-free (GF) mice also received topical LPS challenge and was compared to CON mice.
Topically applied LPS increased expression of IL-1β, TNF-a, and CXCL10 mRNA transcripts in both CON and ABX corneal epithelia compared to vehicle-treated animals, but this response was amplified in the ABX compared to CON group. In conjunctiva, LPS increased expression of IL-1β, IL-6, TNF-a, CXCL10 and IFN-g in both ABX and CON groups compared to vehicle controls. Expression of TNF-a and IFN-g was greater in ABX treated group than CON mice. ABX treatment for 14 days significantly increased MFI of CD86 and MHC II in dendritic cells. After LPS treatment for 4 hours, only the ABX group showed a further increase of CD86 in CD11b+ cells compared to its vehicle. LPS stimulation on GF mice upregulated IL-1β, TNF-a, CXCL10 in corneas and IL-1 β, IL-6, TNF-a, IL-12 IFN-g and CXCL10 compared to its vehicle in conjunctiva. GF mice stimulation produced a 2-fold increase in TNF-a and CXCL10 in cornea compared to LPS-CON mice. A significant higher expression in IL-1 β, IL-6, IFN-g and CXCL10 was noted in LPS-treated GF compared to CON-LPS conjunctiva.
Commensal bacteria modulate TLR4 signaling on the ocular surface, as acute depletion of commensals through antibiotics worsens inflammatory response to LPS. Germ-free mice also display enhanced inflammatory innate response, suggesting that commensal bacterial-derived signals regulate the innate immune inflammatory response and DCs at the ocular surface.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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