Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Understanding hepatic macrophage activation by microbes and microbial components in vivo

Project description

Characterisation of macrophages in the liver

Immune surveillance against microbial insults involves macrophages. Liver-resident macrophages, known as Kupffer cells, are positioned to recognise foreign microbes and, with the help of recruited macrophages, to generate an immune response against infection. The EU-funded MACtivate project is interested to identify the differences between liver resident and recruited macrophages. Using mouse models and human organoids, researchers will investigate the impact of infection on the expression profile and activation of the different macrophage pools. Project results may pave the way for novel therapies that involve the manipulation of these cells.

Objective

Despite playing essential roles in immunity against microbes, the cellular and molecular mechanisms underpinning macrophage (mac) responses to microbial insults remain incompletely understood. In the liver, Kupffer cells (KCs) the tissue-resident macs, reside in the bloodstream of the liver sinusoids and are thus ideally positioned to recognize and phagocytize microbes and microbe-derived components critically contributing to systemic immune surveillance. In addition, KCs are thought to play central roles in maintaining tolerance for example to gut microbiota and/or their products which reach the liver through the portal vein. Upon inflammation/infection, monocytes are also often recruited to liver which, in addition to KCs, participate in immune defence and tissue repair and can differentiate into recruited macs (rMacs). Due to similar expression profiles and functions it has not been possible to unambiguously discriminate between resident KCs and rMacs in the past hampering our understanding of the processes underlying hepatic mac activation by microbes and microbial components. By combining my expertise in host-microbe interactions with the expertise of the host lab in myeloid cell biology, here, I aim to dissect the mac responses to microbial insult in the liver. To achieve this, I will use KC-specific mouse models and human liver organoids combined with novel single cell technologies, with a focus on mac fate, activation profile and tissue context. My preliminary data demonstrate that systemic microbial insult leads to significant heterogeneity within the hepatic mac pool and hence I hypothesize that individual populations may become differentially activated in order to effectively clear microbes and microbial components from the liver. Understanding the processes underpinning mac activation by microbes/microbial products may allow us to manipulate these responses with the ultimate goal of improving patient outcomes.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

See all projects funded under this funding scheme

Call for proposal

(opens in new window) H2020-MSCA-IF-2020

See all projects funded under this call

Coordinator

VIB VZW
Net EU contribution
€ 166 320,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium
Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost
€ 166 320,00