<a name="home"></a>The role of IFN-gamma and IL-4 in gastric mucosa inflammation associated with Helicobacter heilmannii type 1 infection

Abstract

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-γ and IL-4, in H. heilmannii gastric infection in genetically IFN-γ-or IL-4-deficient mice. The serum IFN-γ and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmanniinegative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-γ -/-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-γ 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-γ 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-γ 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-γ playing a central role in gastric inflammation.

Helicobacter heilmannii sensu lato: An overview of the infection in humans

“…Further experimental infections of BALB/c and C57BL/6 mice using 9 H. suis strains, showed that all H. suis isolates induced a predominant T-helper (Th)17 response, but only mild upregulation of the Th2 cytokine interleukin (IL)-4, and no upregulation of Th1 markers, including interferon (IFN)-γ [98] . This contrasts with previously published data which showed that H. suis induced a predominantly Th1 local immune response, and IFN-γ had a major role in the gastric inflammatory process [99,102] . A possible explanation for these differences is that previous experimental infection studies have used homogenized gastric specimens from mice, pigs or non-human primates instead of pure bacterial isolates [99,102] .…”

“…This contrasts with previously published data which showed that H. suis induced a predominantly Th1 local immune response, and IFN-γ had a major role in the gastric inflammatory process [99,102] . A possible explanation for these differences is that previous experimental infection studies have used homogenized gastric specimens from mice, pigs or non-human primates instead of pure bacterial isolates [99,102] .…”

“…Infection with H. felis in these models are often also used to study the pathogenesis of infection and the host immune response to H. pylori [92][93][94][95] . [63,[96][97][98][99] . Experimental infections with H. suis in Mongolian gerbils, BALB/c mice, and C57BL/6 mice showed that while in gerbils H. suis mainly colonized the antrum, in both mice strains H. suis was able to colonize the entire stomach [63] .…”

Virulence factor cytotoxin-associated gene A in Helicobacter pylori is downregulated by interferon-γin vitro

“…Clinical samples show a significantly higher level of IFN-g in H. pylori-infected human gastric mucosa than in uninfected mucosa (Shimizu et al, 2004;Pellicanò et al, 2007), as do animal models (Cinque et al, 2006;Sayi et al, 2009). Clinical samples show a significantly higher level of IFN-g in H. pylori-infected human gastric mucosa than in uninfected mucosa (Shimizu et al, 2004;Pellicanò et al, 2007), as do animal models (Cinque et al, 2006;Sayi et al, 2009).…”

The local immune response of mice after Helicobacter suis infection: strain differences and distinction with Helicobacter pylori

“…Some studies have attempted to characterize the evoked immune response in the mouse, an animal species which has most often been used to model gastric Helicobacter infection. However, because of the fastidious nature of this micro-organism, these experimental infection studies were carried out using impure mucus or homogenized gastric tissue from infected mice, pigs or non-human primates, thus hampering interpretation of these results [18-20]. …”