HEИндивидуална стипендия2023–2025

ReKUPFFERate · Investigating if recuperating hepatic macrophage numbers and functions in chronic fibrosis can limit the incidence and severity of infections

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-10-01 → 2025-09-30
Финансиране от ЕС: 175 920 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Макрофагите в черния дроб се променят при фиброза, което прави пациентите по-податливи на инфекции. Разбирането на тези процеси може да помогне за подобряване на лечението и откриването на инфекции при хора с цироза.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Investigating if recuperating hepatic macrophage numbers and functions in chronic fibrosis can limit the incidence and severity of infections

Liver damage, caused by fibrosis, is the 14th most common cause of death in adults worldwide. In addition to this, it is a major risk factor for infections, where patients with chronic liver fibrosis (cirrhosis) are more likely to acquire infections, and to die from these infections in hospitals, when compared to other patients. As such, this poses a major health burden in Europe and the wider world. The healthy liver is full of immune cells which sit in the bloodstream and constantly survey for damage and infections. One of the cells most suited for this role are the liver resident macrophages. During fibrosis we know that these resident cells are lost and replaced by diverse populations of inflammatory macrophages. We believe that this plays a role in the increased susceptibility to infections in cirrhotic patients. Therefore, in this work this project aimed to understand the following: Identify changes occurring in the immune cells in the fibrotic liver Find genes which can become therapeutic targets in the immune cells Improve the response to infections in cirrhosis via these targets Taken together, this work aimed to improve the understanding of the role of macrophages in the liver during cirrhosis and infections. This was in order to improve the response in patients and lessen the health burden worldwide, both from chronic liver disease and from sepsis, the inappropriate and severe response to infection. This could improve the treatment and detection of infections within cirrhotic patients, leading to new avenues of research and potential targetable mechanisms.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Liver fibrosis is the build-up of scar tissue resulting in impaired liver function. It can have different causes including alcohol abuse, obesity and viral hepatitis. For reasons that we do not fully understand, patients with fibrosis (termed cirrhosis) are more susceptible to infections. In fact, 50% of hospitalized patients with liver cirrhosis and infection die, highlighting the scale of this problem. Macrophages (MFs) are immune cells present in every tissue of the body that function to eliminate pathogens. In the liver, one subset of MFs, the Kupffer cells (KCs) are perfectly equipped with scavenger and pathogen recognition receptors to do this. Moreover, they are positioned in the bloodstream meaning they are one of the first cells to sense and respond to circulating pathogens although their precise roles have not yet been elucidated. In cirrhosis, KCs are reduced in number, being replaced by distinct MF subtypes, including a population termed lipid-associated MFs (LAMs). Preliminary data from the host lab demonstrate that both KCs and LAMs from the cirrhotic liver respond less efficiently to infection when compared with their healthy counterparts. Thus, I hypothesize that the altered MF landscape in cirrhosis and fibrosis is one mechanism driving the increased susceptibility and exacerbated responses to infection in these patients. Here, I aim to test this hypothesis by examining how the different MFs respond to infection in the presence and absence of fibrosis. Using novel mouse models specifically targeting the distinct MF populations, coupled with ex vivo cultures of human hepatic MFs, I will tease apart the mechanisms through which MFs exert their effects and attempt to manipulate these to recuperate normal MF numbers and functions potentially uncovering novel therapeutic approaches to limit infection and improve cirrhotic patient health.

Оригинален текст от CORDIS (на английски).

Участници

VIB VZW · ZWIJNAARDE - GENTКоординаторБелгия