Dataset Information

RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract.

ABSTRACT: Gastrointestinal (GI) nematode infections are an important public health and economic concern. Experimental studies have shown that resistance to infection requires CD4(+) T helper type 2 (Th2) cytokine responses characterized by the production of IL-4 and IL-13. However, despite >30 years of research, it is unclear how the immune system mediates the expulsion of worms from the GI tract. Here, we demonstrate that a recently described intestinal goblet cell-specific protein, RELMbeta/FIZZ2, is induced after exposure to three phylogenetically distinct GI nematode pathogens. Maximal expression of RELMbeta was coincident with the production of Th2 cytokines and host protective immunity, whereas production of the Th1 cytokine, IFN-gamma, inhibited RELMbeta expression and led to chronic infection. Furthermore, whereas induction of RELMbeta was equivalent in nematode-infected wild-type and IL-4-deficient mice, IL-4 receptor-deficient mice showed minimal RELMbeta induction and developed persistent infections, demonstrating a direct role for IL-13 in optimal expression of RELMbeta. Finally, we show that RELMbeta binds to components of the nematode chemosensory apparatus and inhibits chemotaxic function of a parasitic nematode in vitro. Together, these results suggest that intestinal goblet cell-derived RELMbeta may be a novel Th2 cytokine-induced immune-effector molecule in resistance to GI nematode infection.

SUBMITTER: Artis D

PROVIDER: S-EPMC518800 | biostudies-other | 2004 Sep

REPOSITORIES: biostudies-other

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RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract.

Artis David D Wang Mei Lun ML Keilbaugh Sue A SA He Weimian W Brenes Mario M Swain Gary P GP Knight Pamela A PA Donaldson Deborah D DD Lazar Mitchell A MA Miller Hugh R P HR Schad Gerhard A GA Scott Phillip P Wu Gary D GD

Proceedings of the National Academy of Sciences of the United States of America 20040830 37

Gastrointestinal (GI) nematode infections are an important public health and economic concern. Experimental studies have shown that resistance to infection requires CD4(+) T helper type 2 (Th2) cytokine responses characterized by the production of IL-4 and IL-13. However, despite >30 years of research, it is unclear how the immune system mediates the expulsion of worms from the GI tract. Here, we demonstrate that a recently described intestinal goblet cell-specific protein, RELMbeta/FIZZ2, is in ...[more]

PMID: 15340149

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Project description:The chicken gastrointestinal tract (GIT) harbours a complex microbial community, involved in several physiological processes such as host immunomodulation and feed digestion. Other studies were already performed to define the chicken gut metagenome and its fecal metaproteome. For the first time, the present study analysed dietary effects on the protein inventory of the microbiota in crop and ceca of broilers. We performed quantitative label-free metaproteomics by using 1D-gel electrophoresis coupled with LC-MS/MS to identify the structural and functional changes triggered by diets supplied with varying amount of mineral phosphorus (P) and microbial phytase (MP). Phylogenetic assessment based on label-free quantification (LFQ) values of the proteins identified Lactobacillaceae as the major family in the crop section regardless of the diet, whereas proteins belonging to the family Veillonellaceae increased with the P supplementation. Within the ceca section, proteins of Bacteroidaceae were more abundant in the P-supplied diets, whereas proteins of Eubacteriaceae decreased with the P-addition. Proteins of the Ruminococcaceae increasedraised with the amount of MP while proteins of Lactobacillaceae werewas more abundant in the MP-lacking diets. Classification of the identified proteins into COGs and KEGG pathways underlined a diverse microbiota activity depending on the dietary regimen, indicating a thriving microbial community in the case of P and MP supplementation, and stressed microbial community when no P and MP were supplied. Insights oninto the identified KEGG pathways, as well as comparison between the GIT sections, dietary treatments, and the bacterial families encoding for the pathways of interest are provided. T) harbours a complex microbial community, involved in several physiological processes such as host immunomodulation and feed digestion. Other studies were already performed to define the chicken gut metagenome and its fecal metaproteome. For the first time, the present study analysed dietary effects on the protein inventory of the microbiota in crop and ceca of broilers. We performed quantitative label-free metaproteomics by using 1D-gel electrophoresis coupled with LC-MS/MS to identify the structural and functional changes triggered by diets supplied with varying amount of mineral phosphorus (P) and microbial phytase (MP). Phylogenetic assessment based on label-free quantification (LFQ) values of the proteins identified Lactobacillaceae as the major family in the crop section regardless of the diet, whereas proteins belonging to the family Veillonellaceae increased with the P supplementation. Within the ceca section, proteins of Bacteroidaceae were more abundant in the P-supplied diets, whereas proteins of Eubacteriaceae decreased with the P-addition. Proteins of the Ruminococcaceae increasedraised with the amount of MP while proteins of Lactobacillaceae werewas more abundant in the MP-lacking diets. Classification of the identified proteins into COGs and KEGG pathways underlined a diverse microbiota activity depending on the dietary regimen, indicating a thriving microbial community in the case of P and MP supplementation, and stressed microbial community when no P and MP were supplied. Insights oninto the identified KEGG pathways, as well as comparison between the GIT sections, dietary treatments, and the bacterial families encoding for the pathways of interest are provided.

Dataset Information

RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract.

Publications

RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract.

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