Klinik für Pädiatrische Rheumatologie und Immunologie

Immunomodulatory effects of monocytes stimulated by intestinal microbiota: Bacterial factors shaping the innate immune system

The gastrointestinal tract harbours a huge and complex microbial ecosystem, with numbers exceeding 1011 cells per gram of feces. Intestinal epithelial cells (IECs) interact with the intestinal microbiota and vice versa. The communication between IECs and commensal or probiotic bacteria beneficially affects the intestinal barrier function and immune status. Despite the constant stimulation via pattern recognition receptors, intestinal inflammation is prevented by “immune tolerance”. Disruption of this homeostatic state by intruding pathogenic bacteria or inflammatory bowel disease (IBD) can cause impaired barrier function.

In noninflamed mucosa, resident macrophages are anergic but retain avid scavenger and host defense function, an ideal profile for macrophages in close proximity to gut microbiota. However, in the event of impaired epithelial integrity during intestinal infection or inflammation, blood monocytes also accumulate in the lamina propria and actively pursue invading microorganisms through uptake, degradation and release of inflammatory mediators. IBD often arises from a dysregulated mucosal immune response to luminal microorganisms, with translocation and possible replication of bacteria in the submucosal layer. Monocytes/macrophages serve as sentinels, recognizing, ingesting, and destroying the pathogens. If the stimulation of microorganisms cannot be rapidly cleared by intestinal innate immune reactions, adaptive immunity is induced via antigen presentation of monocytes to CD4+ T cells. Thus, monocytes and their derivative cells are the central mediators for both innate and adaptive immunity.

Gut monocytes play a key role in intestinal inflammation but can also be modulated by the microflora. Since monocytes represent cells of high plasticity, the functional consequences of this interaction can vary from pro- to anti-inflammatory effects. We aim to elucidate different microbe-, danger- and pathogen- associated molecular patterns (MAMPs, DAMPs and PAMPs) that are responsible for the differential stimulation of monocytes. For this purpose we investigate different E. coli strains – commensal, probiotic and pathogenic – to elucidate the differential activation of monocytes on a strain-specific level as well as on a virulence factor-dependent level.

 
 
 
 

Project Responsible:
Toni Weinhage, PhD
Markus Brückner, MD