The role of IFN-gamma and IL-4 in gastric mucosa inflammation associated with Helicobacter heilmannii type 1 infection.

Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-gamma and IL-4, in H. heilmannii gastric infection in genetically IFN-gamma- or IL-4-deficient mice. The serum IFN-gamma and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmannii-negative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-gamma(-/-) C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4(-/-) than in WT BALB/c mice. Serum IFN-gamma levels were significantly higher in IL-4(-/-) than in WT BALB/c mice, independently of H. heilmannii-positive or -negative status. Although no difference in serum IFN-gamma levels was seen between H. heilmannii-positive (11.3 +/- 3.07 pg/mL, mean +/- SD) and -negative (11.07 +/- 3.5 pg/mL) WT BALB/c mice, in the group of IL-4(-/-) animals, the serum concentration of IFN-gamma was significantly higher in the infected ones (38.16 +/- 10.5 pg/mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-gamma playing a central role in gastric inflammation.

The role of IFN-gamma and IL-4 in gastric mucosa inflammation associated with Helicobacter heilmannii type 1 infection

Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-gamma and IL-4, in H. heilmannii gastric infection in genetically IFN-gamma- or IL-4-deficient mice. The serum IFN-gamma and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmannii-negative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-gamma-/- C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4-/- than in WT BALB/c mice. Serum IFN-gamma levels were significantly higher in IL-4-/- than in WT BALB/c mice, independently of H. heilmannii-positive or -negative status. Although no difference in serum IFN-gamma levels was seen between H. heilmannii-positive (11.3 ± 3.07 pg/mL, mean ± SD) and -negative (11.07 ± 3.5 pg/mL) WT BALB/c mice, in the group of IL-4-/- animals, the serum concentration of IFN-g was significantly higher in the infected ones (38.16 ± 10.5 pg/mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-gamma playing a central role in gastric inflammation.

Phenotypic study of peripheral blood lymphocytes and humoral immune response in Helicobacter pylori infection according to age.

There are differences between children and adults in certain aspects of the Helicobacter pylori (HP) infection, among them the lower titre of IgG antibodies anti-HP in the former group. Thus, we investigated by means of flow cytometry CD4+/CD3+ (CD4+T), CD8+/CD3+ (CD8+T) and CD19+/CD3- (B) cells, activation/co-stimulatory markers (CD4+/HLA-DR+, CD4+/CD28+, CD8+/HLA-DR+ and CD8+/CD28+) and by means of ELISA IgG anti-HP antibodies in the peripheral blood from HP-positive and -negative children and adults. An increased CD4+/CD28+ and CD8+/CD28+ percentage and number of CD4+/CD3+ cells were seen in infected adults. Conversely, no difference was observed between infected and noninfected children, but when they were stratified by age, an increased CD4+/CD28+ cell percentage was seen in the HP-positive group older than 10 years. The mean level of IgG anti-HP was lower in younger infected children, increased with age and correlated with CD4+ cells. Our data suggest that the immune response to HP infection vary according to the age. Low percentage of activated CD4+ cell may contribute to the lower level of serum IgG anti-HP observed in younger infected children. In addition, the CD4+ cell participation during the infection seems to begin after 10 years old, when the immune response becomes similar to that seen in adults.

Cellular immune responses in Helicobacter heilmannii infection: evaluation of the role of the host and the bacterium.

We evaluated some aspects of the immune response to Helicobacter heilmannii in two mouse strains. Gastritis that was more severe in infected C57BL/6 mice. A proliferative response to H. pylori antigens was observed in splenocytes from H. heilmannii-positive and -negative mice, similar in the positive- and negative-BALB/c mice, but lower in the positive- than in the negative-C57BL/6 animals. A decrease in B cells and an increase in CD4+ cells after stimulation with type I H. pylori antigen and an increase in CD8+ cells after stimulation with type I and II antigens was observed in infected C57BL/6 mice. Conversely, the percentage of CD4+, CD8+, and B cells was similar in positive- and negative-BALB/c mice. These results demonstrated that the immune response is similar in H. heilmannii and H. pylori infection and strengthened the importance of host and bacterial virulence markers in the immune response to gastric Helicobacter infections.

Factors associated with Helicobacter pylori infection by a cagA-positive strain in children.

Although infection with a cagA-positive Helicobacter pylori strain is considered a risk factor for the development of duodenal peptic ulcer in adults, this association has not been demonstrated in children. The presence of cagA was investigated by polymerase chain reaction in H. pylori strains isolated from 27 children with duodenal ulcer and 53 without duodenal ulcer. All patients (100%) with duodenal ulcer and 33 (62.3%) without ulcer were colonized by a cagA-positive strain (P=.00007). A cagA-positive status was also associated with a more marked macroscopic gastritis, with a greater inflammatory infiltrate of both mononuclear and polymorphonuclear cells in the antral and oxyntic gastric mucosae and degenerative and regenerative changes of the gastric mucosa. Increased cagA positivity was also associated with increased age, but no association between cagA-positive status and sex was observed.