ECCO Grant Study Synopsis: Holm Uhlig
Holm Uhlig, ECCO Grant Winner and Sumeet Pandey
Neuro-immune interactions in gut macrophages
© Holm Uhlig
Inflammatory Bowel Diseases (Crohn’s Disease and Ulcerative Colitis) are polygenic and multifactorial disorders caused by aberrant responses to the intestinal microbiota. Crohn’s Disease in particular is associated with defective bacterial handling in phagocytes (i.e. monocytes and macrophages), which digest bacteria by the process known as autophagy/xenophagy. Monocyte/macrophage function is modulated by the surrounding microenviroment, in which pathogens, metabolites, chemokines and cytokines are present.
Interactions between neurons can modulate cytokine production in macrophages. Although there are multiple neurons as well as immune cells within the intestinal compartment that produce neurotransmitters, little is known about how neuro-immune interactions in the gut can also shape human macrophage polarisation, bacterial handling and cytokine response.
We hypothesise that neuro-immune interactions in the gut modulate macrophage function beyond the classical M1/M2 polarisation. We propose to characterise the polarisation of monocyte-derived macrophages treated with neurotransmitters (such as dopamine, histamine, serotonin, noradrenaline and adrenaline) in the presence and absence of bacteria relevant to Crohn’s Disease. We will investigate how the treatment of monocytes and macrophages with neurotransmitters skews the heterogeneity of those cells. Characterisation of M1 and M2 polarisation will be performed by FACS, intracellular cytokine staining and gene expression analysis. In order to investigate the heterogeneity in monocyte/macrophages treated with neurotransmitters at cellular level, we plan to perform single cell RNA sequencing.
The experiments will be performed within a period of one year.