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Understanding hepatic macrophage activation by microbes and microbial components...

Understanding hepatic macrophage activation by microbes and microbial components in vivo 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... ver más

31/03/2023

VLAAMS INSTITUUT...

166K€

Presupuesto del proyecto: 166K€

Líder del proyecto

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2023-03-31

MSCA-IF-2020: Individual Fellowships

I+D

Cerrada hace 4 años

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No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

VLAAMS INSTITUUT BIOTECHNOL...

166.32K€ | Lider

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Duración del proyecto: 24 meses Fecha Inicio: 2021-03-17
Fecha Fin: 2023-03-31

Líder del proyecto

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 166K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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