a-galleria-mellonella-oral-administration-model-to-study-commensal

A <em>Galleria mellonella</em> Oral Administration Model to Study Commensal-Induced Innate Immune Responses

The investigation of the immunogenic potential of commensal bacteria on the host immune system is one essential component when studying intestinal ...

University of Tübingen

Cathepsin S (CTSS) is a lysosomal protease whose activity regulation is important for MHC-II signaling and subsequent activation of CD4(+) T cell mediated immune responses. Dysregulation of its enzymatic activity or enhanced secretion into extracellular environments is associated with the induction or progression of several autoimmune diseases. Here we demonstrate that commensal intestinal bacteria influence secretion rates and intracellular activity of host CTSS and that symbiotic bacteria, i.e. Bacteroides vulgatus mpk, may actively regulate this process and help to maintain physiological levels of CTSS activities in order to prevent from induction of pathological inflammation. The symbiont-controlled regulation of CTSS activity is mediated by anticipating reactive oxygen species induction in dendritic cells which, in turn, maintains cystatin C (CysC) monomer binding to CTSS. CysC monomers are potent endogenous CTSS inhibitors. This Bacteroides vulgatus caused and CysC dependent CTSS activity regulation is involved in the generation of tolerant intestinal dendritic cells contributing to prevention of T-cell mediated induction of colonic inflammation. Taken together, we demonstrate that symbionts of the intestinal microbiota regulate host CTSS activity and secretion and might therefore be an attractive approach to deal with CTSS associated autoimmune diseases.

Symbiotic gut commensal bacteria act as host cathepsin S activity regulators.

It is nowadays generally accepted that the microbiome is a central driver of chronic inflammatory bowel diseases based on observations from human patients as well as inflammatory rodent models. Many studies focussed on different aspects of microbiota and some scientists believe that a primary dis-balance results in a direct microbial induced inflammatory situation. It is also clear that the microbiome is influenced by environmental and genetic factors and is also tightly regulated by host defense molecules such as antimicrobial peptides (defensins et al.). Different lines of investigations showed different complex antimicrobial barrier defects in inflammatory bowel diseases which also influence the composition of the microbiome and generally impact on the microbial-mucosal interface. In this review, we aim to discuss the bigger picture of these different aspects and current views and conclude about therapeutic consequences for future concepts beyond anti-inflammatory treatment.

Microbiome and chronic inflammatory bowel diseases.

The larvae of the greater wax moth, , are pests of active beehives. In infection biology, these larvae are playing a more and more attractive role as an invertebrate host model. Here, we report on the first genome sequence of .

Article	Year
Symbiotic gut commensal bacteria act as host cathepsin S activity regulators. Journal of autoimmunity\| PubMed ID: 27484364	2016
Microbiome and chronic inflammatory bowel diseases. Journal of molecular medicine (Berlin, Germany)\| PubMed ID: 27988792	2017
Genome Sequence of (Greater Wax Moth). Genome announcements\| PubMed ID: 29326202	2018

Julia-Stefanie Frick

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