Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children

C. Serrano; S. W. Wright; D. Bimczok; C. L. Shaffer; T. L. Cover; A. Venegas; M. G. Salazar; L. E. Smythies; P. R. Harris; P. D. Smith

doi:10.1038/mi.2012.133

Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children

C. Serrano, S. W. Wright, D. Bimczok, C. L. Shaffer, T. L. Cover, A. Venegas, M. G. Salazar, L. E. Smythies, P. R. Harris, P. D. Smith

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88 Scopus citations

Abstract

Helicobacter pylori induces less gastric inflammation in children than adults. Here we investigated whether this reduced inflammation involves dysregulated T helper type 17 (Th17) responses. H. pylori-infected children and adults in Santiago, Chile had similar levels of H. pylori colonization, proportions of bacteria containing cagA and s1/s2 vacA markers of virulence, and strain genotypes (predominantly hpEurope), but the children had significantly reduced levels of gastric inflammation and neutrophil infiltration. The reduced neutrophil accumulation in the infected children was accompanied by significantly fewer gastric Th17 cells and significantly lower levels of interleukin (IL)-17-specific mRNA and protein compared with the infected adults. The gastric mucosa of H. pylori-infected children also contained higher numbers of IL-10 + cells and increased levels of both IL-10 and Foxp3 mRNA compared with that of the infected adults. Thus, reduced gastric inflammation, including diminished neutrophil accumulation, in H. pylori-infected children compared with infected adults is likely due to downregulated gastric Th17/IL-17 responses as a consequence of enhanced mucosal regulatory T-cell activity in the children.

Original language	English
Pages (from-to)	950-959
Number of pages	10
Journal	Mucosal Immunology
Volume	6
Issue number	5
DOIs	https://doi.org/10.1038/mi.2012.133
State	Published - Sep 2013

Bibliographical note

Funding Information:
We thank Robin G. Lorenz, M.D., Ph.D. for assistance with the tyramide signal amplification. This study was supported by Fondecyt (#1100654, #1085232) and Conicyt RUE29 (Chile); the National Institutes of Health (DK-54495, DK-84063, AI-83539, AI-83027, RR-20136, AI068009, CA116087, and the Cell and Molecular Pathology Core of the UAB Mucosal HIV and Immunobiology Center, DK-64400); UAB Autoimmunity, Immunology and Transplantation Pilot Program; UAB Center for Clinical and Translational Science Pilot Program (UL1, TR000165); the Department of Veterans Affairs; and the Fulbright Fellowship Program, Department of State (USA).

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/mi.2012.133

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title = "Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children",

abstract = "Helicobacter pylori induces less gastric inflammation in children than adults. Here we investigated whether this reduced inflammation involves dysregulated T helper type 17 (Th17) responses. H. pylori-infected children and adults in Santiago, Chile had similar levels of H. pylori colonization, proportions of bacteria containing cagA and s1/s2 vacA markers of virulence, and strain genotypes (predominantly hpEurope), but the children had significantly reduced levels of gastric inflammation and neutrophil infiltration. The reduced neutrophil accumulation in the infected children was accompanied by significantly fewer gastric Th17 cells and significantly lower levels of interleukin (IL)-17-specific mRNA and protein compared with the infected adults. The gastric mucosa of H. pylori-infected children also contained higher numbers of IL-10 + cells and increased levels of both IL-10 and Foxp3 mRNA compared with that of the infected adults. Thus, reduced gastric inflammation, including diminished neutrophil accumulation, in H. pylori-infected children compared with infected adults is likely due to downregulated gastric Th17/IL-17 responses as a consequence of enhanced mucosal regulatory T-cell activity in the children.",

author = "C. Serrano and Wright, {S. W.} and D. Bimczok and Shaffer, {C. L.} and Cover, {T. L.} and A. Venegas and Salazar, {M. G.} and Smythies, {L. E.} and Harris, {P. R.} and Smith, {P. D.}",

note = "Funding Information: We thank Robin G. Lorenz, M.D., Ph.D. for assistance with the tyramide signal amplification. This study was supported by Fondecyt (#1100654, #1085232) and Conicyt RUE29 (Chile); the National Institutes of Health (DK-54495, DK-84063, AI-83539, AI-83027, RR-20136, AI068009, CA116087, and the Cell and Molecular Pathology Core of the UAB Mucosal HIV and Immunobiology Center, DK-64400); UAB Autoimmunity, Immunology and Transplantation Pilot Program; UAB Center for Clinical and Translational Science Pilot Program (UL1, TR000165); the Department of Veterans Affairs; and the Fulbright Fellowship Program, Department of State (USA).",

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AU - Serrano, C.

AU - Wright, S. W.

AU - Bimczok, D.

AU - Shaffer, C. L.

AU - Cover, T. L.

AU - Venegas, A.

AU - Salazar, M. G.

AU - Smythies, L. E.

AU - Harris, P. R.

AU - Smith, P. D.

N1 - Funding Information: We thank Robin G. Lorenz, M.D., Ph.D. for assistance with the tyramide signal amplification. This study was supported by Fondecyt (#1100654, #1085232) and Conicyt RUE29 (Chile); the National Institutes of Health (DK-54495, DK-84063, AI-83539, AI-83027, RR-20136, AI068009, CA116087, and the Cell and Molecular Pathology Core of the UAB Mucosal HIV and Immunobiology Center, DK-64400); UAB Autoimmunity, Immunology and Transplantation Pilot Program; UAB Center for Clinical and Translational Science Pilot Program (UL1, TR000165); the Department of Veterans Affairs; and the Fulbright Fellowship Program, Department of State (USA).

PY - 2013/9

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N2 - Helicobacter pylori induces less gastric inflammation in children than adults. Here we investigated whether this reduced inflammation involves dysregulated T helper type 17 (Th17) responses. H. pylori-infected children and adults in Santiago, Chile had similar levels of H. pylori colonization, proportions of bacteria containing cagA and s1/s2 vacA markers of virulence, and strain genotypes (predominantly hpEurope), but the children had significantly reduced levels of gastric inflammation and neutrophil infiltration. The reduced neutrophil accumulation in the infected children was accompanied by significantly fewer gastric Th17 cells and significantly lower levels of interleukin (IL)-17-specific mRNA and protein compared with the infected adults. The gastric mucosa of H. pylori-infected children also contained higher numbers of IL-10 + cells and increased levels of both IL-10 and Foxp3 mRNA compared with that of the infected adults. Thus, reduced gastric inflammation, including diminished neutrophil accumulation, in H. pylori-infected children compared with infected adults is likely due to downregulated gastric Th17/IL-17 responses as a consequence of enhanced mucosal regulatory T-cell activity in the children.

AB - Helicobacter pylori induces less gastric inflammation in children than adults. Here we investigated whether this reduced inflammation involves dysregulated T helper type 17 (Th17) responses. H. pylori-infected children and adults in Santiago, Chile had similar levels of H. pylori colonization, proportions of bacteria containing cagA and s1/s2 vacA markers of virulence, and strain genotypes (predominantly hpEurope), but the children had significantly reduced levels of gastric inflammation and neutrophil infiltration. The reduced neutrophil accumulation in the infected children was accompanied by significantly fewer gastric Th17 cells and significantly lower levels of interleukin (IL)-17-specific mRNA and protein compared with the infected adults. The gastric mucosa of H. pylori-infected children also contained higher numbers of IL-10 + cells and increased levels of both IL-10 and Foxp3 mRNA compared with that of the infected adults. Thus, reduced gastric inflammation, including diminished neutrophil accumulation, in H. pylori-infected children compared with infected adults is likely due to downregulated gastric Th17/IL-17 responses as a consequence of enhanced mucosal regulatory T-cell activity in the children.

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Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children

Abstract

Bibliographical note

ASJC Scopus subject areas

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