The Th1/Th17 literature is similarly confusing with respect to H. pylori-associated gastric pathology. Sayi et al. and Stoicov et al. found that IFN-γ production by T cells and expression of the Th1-lineage-committing transcription factor T-bet were required for H. pylori-induced gastric preneoplasia [21,22]. Similarly, Sheh et al. [23] noted an increased mutation frequency in the H. pylori-infected gastric mucosa and attributed this to H. pylori-specific Th1 responses and prolonged exposure to oxidative stress. Arguing that Th17 rather than selleck chemicals llc Th1 cells are important drivers in H. pylori-induced gastritis, Shi et al. [24] reported that both IL-17 neutralization and IL-17 gene targeting

reduced gastric inflammation. Complicating the issue further, the groups of Otani et al. and Algood et al. each detected more, rather than less, gastric inflammation upon IL-17 neutralization [25] and in IL-17A receptor gene-targeted mice [26]. In humans, the notion that Th1 cells constitute

the predominant Th population was verified once again in an impressive longitudinal study by Perez-Perez et al. [27] that examined IgG subclass responses in paired serum samples obtained in 1973 and in 1994 from H. pylori-infected, healthy donors. Most PD0325901 manufacturer (89%) donors exhibited IgG1/IgG4 ratios that were consistent with a predominant Th1 response and were remarkably stable over the 21-year period [27]. Although the Th1-predominant response to H. pylori is largely ineffective in clearing the infection, it may have unanticipated positive side effects in the prevention or suppression of coinfections. The groups of Parsonnet, Solnick, and Flynn recently presented evidence from H. pylori-infected humans and cynomolgus macaques showing that the Th1 response to H. pylori may have beneficial bystander effects on a coexisting Mycobacterium tuberculosis infection [28]. The initial hint of an inverse correlation between active tuberculosis

and H. pylori came from the observation that IFN-γ responses to M. tuberculosis antigen were 1.5-fold stronger in H. pylori-infected individuals with positive tuberculin skin tests (i.e., latent tuberculosis infection, selleck chemicals LTBI) than in their H. pylori-negative counterparts [28]. Follow-up studies comparing the H. pylori infection status of active tuberculosis cases and non-progressing household contacts revealed a significantly higher H. pylori seroprevalence in the latter group. This finding was corroborated by a significant inverse relationship between natural H. pylori infection and active tuberculosis in cynomolgus macaques challenged with M. tuberculosis [28]. Experimental studies in non-human primates will be required to confirm these observational data. The marked diversity of clinical isolates of H. pylori has been attributed to genomic changes that occur during its lifelong adaptation to human hosts.