A significantly higher expression of pSmad2/3L-Thr in specific epithelial cells in the gastric mucosa of H. felis-infected mice with gastritis could be found. The authors suggested that these cells might be epithelial stem cells [41]. Undoubtedly, one of the most exciting articles published this year in the field came from Chow and Mazmanian [42]. Using an elegant intestinal epithelial cell coculture model coupled with adoptive cell transfer studies, it was shown that the H. hepaticus type VI secretion system (T6SS) appears to promote a symbiotic relationship between the microbe and host. Presence of the

T6SS was demonstrated to limit intestinal epithelial cell invasion and also to elicit anti-inflammatory activity aimed at promoting a balanced relationship with the host. H. hepaticus

has also been shown to modulate constitutive macrophage responses to make them more anti-inflammatory, MG-132 price increasingly phagocytic, and resistant to secondary stimulation [43]. A second study also showed that H. hepaticus could alter TLR4 adaptor protein usage and demonstrated distinct roles for MyD88 and Trif signaling pathways in the context of intestinal ischemia–reperfusion (IR) in the presence of H. hepaticus infection [44]. A similar finding was also demonstrated in a model of hemorrhage-induced tissue damage with H. hepaticus infection shown to modulate the mechanism of intestinal damage and inflammation [45]. In early 2010, Fox et al. STK38 [46] also reported that H. hepaticus infection could promote Imatinib price liver tumors in hepatitis C transgenic mice. The study showed that H. hepaticus colonization of the intestine could promote HCV- and aflatoxin-induced tumors with NF-kB signaling identified as pivotal to the process. This work was followed by the identification that Helicobacter marmotae-associated inflammation could also act as a tumor promoter [47]. Interestingly, in contrast to the previous H. hepaticus studies, H. marmotae-associated hepatic lesions

did not progress as extensively with no evidence of hyperplasia or necrosis detected. Differences in the pathogenic capabilities of Helicobacter species have been documented previously in some cases resulting in opposing effects in a specific disease model [48]. Further evidence to support these differential responses was provided through a study by Eaton et al. [49]. A Helicobacter-infected Smad3 knockout mouse model used for therapeutic colorectal cancer studies was investigated for its usefulness in identifying early stage disease including potentially prior to disease onset [50]. Noncontrast-enhanced MRI could detect MUC lesions in 58% of histologically confirmed cases at 8 weeks postinfection; however, serial imaging produced inconsistent results.