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Effects of flagellin on the functions of follicle-associated epithelium.

ABSTRACT: Bacterial flagellin activates innate immune responses by signaling through Toll-like receptor 5 and is a potential vaccine adjuvant. Mucosal lymphoid follicles, inductive sites for adaptive mucosal immune responses, are covered by a follicle-associated epithelium (FAE) specialized for the uptake of antigens. This study demonstrates that mucosal application of Salmonella dublin flagellin enhanced transepithelial transport of microparticles by the FAE of mouse Peyer's patches in vivo. Flagellin also induced rapid, matrix metalloproteinase-dependent migration of subepithelial dendritic cells (DCs) into the FAE, better positioning DCs for antigen capture. These innate responses to flagellin enhance FAE functions and may promote adaptive immune responses in the mucosa.

SUBMITTER: Chabot SM

PROVIDER: S-EPMC5037956 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Effects of flagellin on the functions of follicle-associated epithelium.

Chabot Sophie M SM Shawi May M Eaves-Pyles Tonyia T Neutra Marian R MR

The Journal of infectious diseases 20080901 6

Bacterial flagellin activates innate immune responses by signaling through Toll-like receptor 5 and is a potential vaccine adjuvant. Mucosal lymphoid follicles, inductive sites for adaptive mucosal immune responses, are covered by a follicle-associated epithelium (FAE) specialized for the uptake of antigens. This study demonstrates that mucosal application of Salmonella dublin flagellin enhanced transepithelial transport of microparticles by the FAE of mouse Peyer's patches in vivo. Flagellin al ...[more]

PMID: 18721059

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Project description:The follicle-associated epithelium (FAE) is a specialized structure that samples luminal antigens and transports them into mucosa-associated lymphoid tissues (MALT). In mammals, transcytosis of antigens across the gut epithelium is performed by a subset of FAE cells known as M cells. Here we show that colony-stimulating factor 1 receptor (CSF1R) is expressed by a subset of cells in the avian bursa of Fabricius FAE. Expression was initially detected using a CSF1R-reporter transgene that also label subsets of bursal macrophages. Immunohistochemical detection using a specific monoclonal antibody confirmed abundant expression of CSF1R on the basolateral membrane of FAE cells. CSF1R-transgene expressing bursal FAE cells were enriched for expression of markers previously reported as putative M cell markers, including annexin A10 and CD44. They were further distinguished from a population of CSF1R-transgene negative epithelial cells within FAE by high apical F-actin expression and differential staining with the lectins jacalin, PHA-L and SNA. Bursal FAE cells that express the CSF1R-reporter transgene were responsible for the bulk of FAE transcytosis of labeled microparticles in the size range 0.02-0.1 μm. Unlike mammalian M cells, they did not readily take up larger bacterial sized microparticles (0.5 μm). Their role in uptake of bacteria was tested using Salmonella, which can enter via M cells in mammals. Labeled Salmonella enterica serovar Typhimurium entered bursal tissue via the FAE. Entry was partially dependent upon Type III secretion system-1. However, the majority of invading bacteria were localized to CSF1R-negative FAE cells and in resident phagocytes that express the phosphatidylserine receptor TIM4. CSF1R-expressing FAE cells in infected follicles showed evidence of cell death and shedding into the bursal lumen. In mammals, CSF1R expression in the gut is restricted to macrophages which only indirectly control M cell differentiation. The novel expression of CSF1R in birds suggests that these functional equivalents to mammalian M cells may have different ontological origins and their development and function are likely to be regulated by different growth factors.

Dataset Information

Effects of flagellin on the functions of follicle-associated epithelium.

Publications

Effects of flagellin on the functions of follicle-associated epithelium.

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