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Final Report Summary - INFLACOMM (Interplay of inflammasomes, commensals and pathogens at mucosal interfaces)

Humans are colonized and surrounded by complex microbial ecosystems containing many microbes beneficial to human health, but also ones that are able to cause serious diseases. The host’s innate immune system plays a vital role in the decision-making on whether to combat a specific microbe, i.e. raise an inflammatory response, or whether to ignore them, i.e. maintain a tolerogenic environment. Evidence from numerous studies suggests that dysregulated or impaired innate immune responses are significantly contributing to diseases with significant impact on human health including Inflammatory Bowel Diseases (IBD) and Rheumatoid Arthritis, however the contribution of specific receptors and pathways has only been partially solved.
The objectives of the ongoing research funded by the CIG in my “Young Investigator Group” at the Helmholtz Centre for Infection Research is to elucidate the contribution of a specific family of innate receptors, that share the ability to induce formation of so-called inflammasomes, in intestinal homeostasis and inflammation. Inflammasomes are platforms regulating the activity of the protease caspase-1, which controls the release of proinflammatory cytokines and is able to induce a specific form of inflammatory cell death. Conflicting results had been reported regarding their function in intestinal inflammation in mouse models of IBD. Our current results suggest that the outcomes of these experiments are strongly influenced by the composition of the intestinal microbiota and by complex interactions of caspase-1 and a related protease, caspase-11.
Funding though CIG has been instrumental in setting up my research group by providing funds to recruit a graduate student and to establish this project, whose interesting results we successfully published (Blazejewski et al, Cell Reports 2017). These results are likely to have a wider impact on how to characterize animal models of complex diseases including, but not limited to, IBD.

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