3). No relationship was found between cytokines and bacteria in the lungs except a positive association between IL-4 and bacterial numbers in the dual B. bronchiseptica–G. strigosum infection (coeff±SE: 0.889±0.216 P=0.003)

( Fig. 3A). Similarly, no significant relationships were found for G. AZD2281 in vitro strigosum except a positive relationship between IFN-γ and the helminth in the fundus (7.230±2.378×0.038) ( Fig. 3B). In the small intestine, T. retortaeformis intensity was positively associated with IFN-γ (0.579±0.070 P<0.0001), IL-10 (0.124±0.054 P=0.037) and IL-4 (only when interacting with the dual helminth infection: 0.236±0.104 P=0.043) ( Fig. 3C). The analysis repeated independently for the duodenum and the ileum showed a significant negative relationship between helminth abundance and IL-4 (−0.966±0.253 P=0.002) and IL-10 (−0.533±0.248 P=0.0498) in the duodenum; no significant associations

were observed in the ileum. A snapshot at day seven post challenge of cytokine gene expression in a number of relevant organs and across a combination of infections with a respiratory bacterium and two gastrointestinal helminths revealed two main patterns. First, the level of local IFN-γ, IL-4 and IL-10 expression in a specific organ was affected by the type and number of co-infections occurring in other organs; this bystander effect was more apparent in some organs than others and not for every cytokine measured. TGF-beta inhibitor Specifically, IFN-γ against B. bronchiseptica in the lungs was suppressed by helminth co-infections, the expression of the three cytokines against G. strigosum in the stomach were also suppressed in hosts concurrently infected with B. bronchiseptica, while the cytokine response against T. retortaeformis in the small intestine was generally augmented in the presence of co-infections. Second, within the same organ, relative cytokine expression was consistent across different infections and exhibited a general positive trend. In other words, a second NADPH-cytochrome-c2 reductase pathogen altered cytokine expression

levels against the first pathogen in another organ, but not the positive relationship between cytokines. These findings suggest that there is relatively low tissue compartmentalization among the organs examined. However, while some organs are more sensitive to bystander effects than others, they appear to adjust the cytokine pool to levels that avoid immuno-pathology. Indeed, the positive correlation between cytokines among infections from the same organ is indicative of cross-regulation between these cytokines. Interestingly, baseline cytokine expression in the uninfected stomach and small intestine suggests that there are relatively weak bystander signals in these organs in the absence of active infections. Mutual regulation between IFN-γ, IL-4 and IL-10 has been well-characterized for T. muris and S.