Helicobacter pylori Gastritis in Children Is Associated With a Regulatory T-Cell Response

Harris, Paul; Wright, Shelton W.; Serrano, Carolina; Riera, Francisca; Duarte, Ignacio; Torres, Javiera; Peña, Alfredo; Rollán, Antonio; Viviani, Paola; Guiraldes, Ernesto; Schmitz, Júlia; Lorenz, Robin G.; Novak, Lea; Smythies, Lesley E.; Smith, Phillip D.

doi:10.1053/j.gastro.2007.11.006

Cited by 204 publications

(207 citation statements)

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“…24 Emerging clinical evidence of an enhanced regulatory T cell (Treg) response in the H. pylori-infected stomach that correlates with mucosal tolerance in children implicates the critical role of mucosal Tregs in disease modulation. 25 In our article published in Gastroenterology, 26 we provided evidence to support the hypothesis that an interaction between H. pylori and mucosal DCs leads to the higher Treg response observed in H. pylori-infected patients. 25,27 We first nonintegrin (DC-SIGN) is the DC surface receptor that binds H. pylori glycans 11,12 and that H. pylori stimulates DCs predominantly through a Toll-like receptor (TLR)-dependent signaling cascade.…”

Section: Helicobacter Pylori Directs Tolerogenic Programming Of Dendrmentioning

confidence: 62%

“…25 In our article published in Gastroenterology, 26 we provided evidence to support the hypothesis that an interaction between H. pylori and mucosal DCs leads to the higher Treg response observed in H. pylori-infected patients. 25,27 We first nonintegrin (DC-SIGN) is the DC surface receptor that binds H. pylori glycans 11,12 and that H. pylori stimulates DCs predominantly through a Toll-like receptor (TLR)-dependent signaling cascade. 13 H. pylori-pulsed DCs (HP-DC) promote a type 1 helper T cell (Th1) response [14][15][16][17][18][19][20] and, as shown more recently, an interleukin (IL)-17-producing helper T cell (Th17) response.…”

Section: Helicobacter Pylori Directs Tolerogenic Programming Of Dendrmentioning

confidence: 62%

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Helicobacter pyloridirects tolerogenic programming of dendritic cells

et al. 2010

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3 Gastric CD103 + dendritic cells, which are known to induce mucosal regulatory T cells, were also increased in number, raising the question whether H. pylori infection induces a regulatory T cell-skewed response by way of a bacteria-dendritic cell interaction. In fact, bone marrow-derived dendritic cells underwent tolerogenic programming, skewing the balance between effector and regulatory T cell responses towards regulatory T cell differentiation in a transforming growth factor-β-and interleukin-10-dependent manner. Depletion of regulatory T cell numbers augmented H. pylorispecific effector helper T cell responses, which correlated with a lower degree of H. pylori colonization. These results suggest H. pylori is capable of inducing a regulatory T cell-skewed response that limits the host's ability to eradicate the bacteria, allowing the H. pylori infection to persist. To better understand the mechanism of H. pylori tolerogenic programming we compared the differential expressions of 34 genes critical for dendritic cell function in bone marrowderived dendritic cells pulsed with live H. pylori or other Gram-negative bacteria (e.g., Escherichia coli, Acinetobacter lwoffii). Our data imply that H. pylori targets the Toll-like receptor 2 pathway to induce a regulatory T cell-skewed response. In addition, we show that H.

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Section: Helicobacter Pylori Directs Tolerogenic Programming Of Dendrmentioning

confidence: 62%

Section: Helicobacter Pylori Directs Tolerogenic Programming Of Dendrmentioning

confidence: 62%

Helicobacter pyloridirects tolerogenic programming of dendritic cells

et al. 2010

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“…Previous studies (Tiwari et al 2005, Loster et al 2006, Souto & Colombo 2008, Harris et al 2008) used PCR to diagnose an infection of H. pylori. These results are comparable to the results of the present study, in which there was a 95% success rate in the detection of H. pylori in the stomach.…”

Section: Detection Of H Pylori In Saliva and Dental Plaque By Southementioning

confidence: 99%

Helicobacter pylori detection in gastric biopsies, saliva and dental plaque of Brazilian dyspeptic patients

Rasmussen

Lábio

Gatti

et al. 2010

Mem. Inst. Oswaldo Cruz

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Helicobacter pylori is an important human pathogen that causes chronic gastritis and is associated with the development of peptic ulcer disease and gastric malignancies. The oral cavity has been implicated as a potential H. pylori reservoir and may therefore be involved in the reinfection of the stomach, which can sometimes occur following treatment of an H. pylori infection. The objectives of this paper were (i) to determine the presence of H. pylori in the oral cavity and (ii) to examine the relationship between oral H. pylori and subsequent gastritis. Gastric biopsies, saliva samples and dental plaques were obtained from 78 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori using polymerase chain reaction and Southern blotting methods. Persons with gastritis were frequently positive for H. pylori in their stomachs (p < 0.0001) and there was a statistically significant correlation between the presence of H. pylori in gastric biopsies and the oral cavity (p < 0.0001). Our results suggest a relationship between gastric infection and the presence of this bacterium in the oral cavity. Despite this, H. pylori were present in the oral cavity with variable distribution between saliva and dental plaques, suggesting the existence of a reservoir for the species and a potential association with gastric reinfection

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“…H. pylori has colonized its human host for at least 60,000 y (7) and during this long period of coevolution has evolved elaborate ways to systemically manipulate adaptive immune responses and to promote its persistence through the preferential induction of regulatory T-cell (Treg) over T-effector cell responses. Treg-predominant responses are characteristic of heavily colonized but asymptomatic carriers (4) and of children with particularly mild forms of Helicobacter-associated gastritis (8). Several recent functional studies using experimentally infected animals have implicated Tregs and dendritic cells (DCs) with "tolerogenic" activity in mediating the local and systemic immunomodulatory effects of H. pylori infection (9-12).…”

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confidence: 99%

Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance

Oertli

Noben

Engler

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

208

190

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Infection with the gastric bacterial pathogen Helicobacter pylori is typically contracted in early childhood and often persists for decades. The immunomodulatory properties of H. pylori that allow it to colonize humans persistently are believed to also account for H. pylori's protective effects against allergic and chronic inflammatory diseases. H. pylori infection efficiently reprograms dendritic cells (DCs) toward a tolerogenic phenotype and induces regulatory T cells (Tregs) with highly suppressive activity in models of allergen-induced asthma. We show here that two H. pylori virulence determinants, the γ-glutamyl transpeptidase GGT and the vacuolating cytotoxin VacA, contribute critically and nonredundantly to H. pylori's tolerizing effects on murine DCs in vitro and in vivo. The tolerancepromoting effects of both factors are independent of their described suppressive activity on T cells. Isogenic H. pylori mutants lacking either GGT or VacA are incapable of preventing LPS-induced DC maturation and fail to drive DC tolerization as assessed by induction of Treg properties in cocultured naive T cells. The Δggt and ΔvacA mutants colonize mice at significantly reduced levels, induce stronger T-helper 1 (Th1) and T-helper 17 (Th17) responses, and/or trigger more severe gastric pathology. Both factors promote the efficient induction of Tregs in vivo, and VacA is required to prevent allergen-induced asthma. The defects of the Δggt mutant in vitro and in vivo are phenocopied by pharmacological inhibition of the transpeptidase activity of GGT in all readouts. In conclusion, our results reveal the molecular players and mechanistic basis for H. pyloriinduced immunomodulation, promoting persistent infection and conferring protection against allergic asthma.bacterial virulence factors | hygiene hypothesis | persistent bacterial infection | human microbiota | persistence strategies T he bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans. It is typically acquired in early childhood (1) and, in the absence of antibiotic therapy, may persist for the entire lifespan of the host (2, 3). The extraordinary ability of H. pylori to resist a vigorous adaptive immune response driven in large part by T-helper 1 (Th1) and/or T-helper 17 (Th17)-polarized effector T cells (4, 5) has been attributed to its perfect adaptation to-and manipulation of-the human innate and adaptive immune systems (6). H. pylori has colonized its human host for at least 60,000 y (7) and during this long period of coevolution has evolved elaborate ways to systemically manipulate adaptive immune responses and to promote its persistence through the preferential induction of regulatory T-cell (Treg) over T-effector cell responses. Treg-predominant responses are characteristic of heavily colonized but asymptomatic carriers (4) and of children with particularly mild forms of Helicobacter-associated gastritis (8). Several recent functional studies using experimentally infected animals have implicated Tregs and dendritic cells (...

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Helicobacter pylori Gastritis in Children Is Associated With a Regulatory T-Cell Response

Cited by 204 publications

References 46 publications

Helicobacter pyloridirects tolerogenic programming of dendritic cells

Helicobacter pyloridirects tolerogenic programming of dendritic cells

Helicobacter pylori detection in gastric biopsies, saliva and dental plaque of Brazilian dyspeptic patients

Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance

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