Immune and Proliferative Cellular Responses to Helicobacter pylori Infection in the Gastric Mucosa of Mexican Children

Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, México City, México.
Helicobacter (Impact Factor: 4.11). 07/2007; 12(3):224-30. DOI: 10.1111/j.1523-5378.2007.00493.x
Source: PubMed


Helicobacter pylori infection occurs mostly during childhood, but few studies on this age group have addressed the innate immune and the proliferative response to this infection. Mexico has a high H. pylori prevalence in children, but a low risk of gastric cancer. The aim of this work was to study the cellular responses of the gastric mucosa to this infection in Mexican children.
Antral and corpus gastric biopsies were obtained from 44 H. pylori-infected children (mean age 12 +/- 3.2 years) and 44 uninfected children (mean age 10 +/- 3 years). Mucosal cellular responses were studied by immunohistochemistry, using anti-Ki67 antibodies for proliferation studies, antihuman tryptase for mast cells, and antihuman CD68 for macrophages. T and B lymphocytes were stained with a commercial integrated system. The intensity of cellular responses was estimated histologically using the software KS300.
Epithelium proliferation and infiltration of macrophages and T and B lymphocytes were significantly higher in H. pylori-infected than in uninfected children. A balanced increase of CD4, CD8, and CD20 lymphocytes was observed in infected children. However, activated mast cells were decreased, and infiltration of neutrophil and mononuclear cells was low. Epithelial proliferation was associated with polymorphonuclear infiltration but not with infiltration of macrophages or lymphocytes. Inflammation and proliferation was higher in CagA (+)-infected children.
Mexican children respond to H. pylori infection with a low inflammatory response, a balanced increase of T and B lymphocytes, and a high regenerative activity.

Download full-text


Available from: Javier Torres, Oct 22, 2014
23 Reads
  • Source
    • "This appears to be a characteristic feature of H. pylori infection, as gastric mucosal cell proliferation is increased in H. pyloriassociated chronic gastritis but not in chronic gastritis where the organism is absent (Lynch et al., 1995). Study by Munoz et al. (2007) also suggests proliferative activity as the epithelial regenerative response to cell damage caused by inflammatory mediators. The initiation of an active inflammatory response. "
    [Show abstract] [Hide abstract]
    ABSTRACT: H. pylori is a major etiological agent in the development of various gastro-duodenal diseases. Its persistence in gastric mucosa is determined by the interaction between various host, microbial and environmental factors. The bacteria colonizes the gastric epithelium and induces activation of various chemokine mediators, including NFKB, the master regulator of inflammation. H. pylori infection is also associated with an increase in expression of cell cycle regulators thereby leading to mucosal cell hyper proliferation. Thus, H. pylori-associated infections manifest activation of key host response events, which inadvertently could lead to the establishment of chronic infection and neoplastic progression. This article reviews and elaborates the current knowledge in H. pylori induced activation of various host signaling pathways that could promote cancer development. Special focus is placed on the inflammatory and proliferative responses that could serve as suitable biomarkers of infection, since a sustained cell proliferation in an environment rich in inflammatory cells is characteristic in H. pylori-associated gastric malignancies. Here, the role of ERK and WNT signaling in H. pylori-induced activation of inflammatory and proliferative responses respectively is discussed in detail. An in depth analysis of the underlying signaling pathways and interacting partners causing alterations in these crucial host responses could contribute to the development of successful therapeutic strategies for the prevention, management and treatment of H. pylori infection.
    Microbiology 02/2015; 161(6). DOI:10.1099/mic.0.000066 · 2.56 Impact Factor
  • Source
    • "There is little information on the induction of local immune responses in the gastric mucosa from children (39, 40). Few studies have evaluated the cytokine responses in the gastric mucosa of this age group and the results are contradictory (17, 41, 42). "
    [Show abstract] [Hide abstract]
    ABSTRACT: T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell isolation method that yielded high numbers of viable lamina propria mononuclear cells (LPMC) from gastric biopsies. Classic memory T subsets were identified in gastric LPMC and compared to peripheral blood mononuclear cells (PBMC) obtained from children, adults, and the elderly using an optimized 14 color flow cytometry panel. A dominant effector memory T (TEM) phenotype was observed in gastric LPMC CD4(+) and CD8(+) T cells in all age groups. We then evaluated whether these cells represented a population of gastric tissue-resident memory T (TRM) cells by assessing expression of CD103 and CD69. The vast majority of gastric LPMC CD8(+) T cells either co-expressed CD103/CD69 (>70%) or expressed CD103 alone (~20%). Gastric LPMC CD4(+) T cells also either co-expressed CD103/CD69 (>35%) or expressed at least one of these markers. Thus, gastric LPMC CD8(+) and CD4(+) T cells had the characteristics of TRM cells. Gastric CD8(+) and CD4(+) TRM cells produced multiple cytokines (IFN-γ, IL-2, TNF-α, IL-17A, MIP-1β) and up-regulated CD107a upon stimulation. However, marked differences were observed in their cytokine and multi-cytokine profiles when compared to their PBMC TEM counterparts. Furthermore, gastric CD8(+) TRM and CD4(+) TRM cells demonstrated differences in the frequency, susceptibility to activation, and cytokine/multi-cytokine production profiles among the age groups. Most notably, children's gastric TRM cells responded differently to stimuli than gastric TRM cells from adults or the elderly. In conclusion, we demonstrate the presence of gastric TRM, which exhibit diverse functional characteristics in children, adults, and the elderly.
    Frontiers in Immunology 06/2014; 5:294. DOI:10.3389/fimmu.2014.00294
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Helicobacter pylori strains display remarkable genetic diversity, and the presence of strains bearing the toxigenic vacA s1 allele, a complete cag pathogenicity island (PAI), cagA alleles containing multiple EPIYA phosphorylation sites, and expressing the BabA adhesin correlates with development of gastroduodenal disease in adults. To better understand the genetic variability present among pediatric strains and its relationship to disease, we characterized H. pylori strains infecting 47 pediatric North American patients. Prevalence of mixed infection was assessed by random amplified polymorphic DNA analysis of multiple H. pylori clones from each patient. Microarray-based comparative genomic hybridization was used to examine the genomic content of the pediatric strains. The cagA and vacA alleles were further characterized by allele-specific PCR. A range of EPIYA motif configurations were observed for the cagA gene, which was present in strains from 22 patients (47%), but only 19 (41%) patients contained a complete cag PAI. Thirty patients (64%) were infected with a strain having the vacA s1 allele, and 28 patients (60%) had the babA gene. The presence of a functional cag PAI was correlated with ulcer disease (P = 0.0095). In spite of declining rates of H. pylori infection in North America, at least 11% of patients had mixed infection. Pediatric strains differ in their spectrum of strain-variable genes and percentage of absent genes in comparison to adult strains. Most children were infected with H. pylori strains lacking the cag PAI, but the presence of a complete cag PAI, in contrast to other virulence markers, was associated with more severe gastroduodenal disease.
    Journal of clinical microbiology 05/2009; 47(6):1680-8. DOI:10.1128/JCM.00273-09 · 3.99 Impact Factor
Show more