H2020Индивидуална стипендия2018–2020

BREFMC2017 · Deciphering the function(s) of the C-type lectin DCIR/CLEC4A in tuberculosis

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-06-01 → 2020-05-31
Финансиране от ЕС: 173 076 €
Участници: 1
Схема: MSCA-IF-EF-ST

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Накратко на български

Рецепторът DCIR в имунните клетки се изследва за това как регулира отговора на организма при туберкулоза. Разбирането на този механизъм помага да се разбере балансът между защитата срещу бактериите и възпалението в белите дробове.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Deciphering the function(s) of the C-type lectin DCIR/CLEC4A in tuberculosis

Tuberculosis (TB), caused by the infectious agent Mycobacterium tuberculosis (Mtb), is a devastating disease and one of the leading causes of death in the developing world. Immune cells play a key role in anti-mycobacterial immunity and express a range of pattern-recognition receptors, which are involved in the recognition of Mtb antigens. Dr Neyrolles’ lab has characterised a number of these receptors, with the most recent being, and the focus of this project, the Dendritic Cell Immunoreceptor (DCIR) with the aim of deciphering its role in Mtb immunity. They have demonstrated that when compared to wild-type (WT) mice, mice inactivated in the DCIR homolog (mDCIR1-KO) display increased antimycobacterial immunity as a result of an impaired response to type I interferon and an increased production of IL-12. Consequently, mDCIR1-KO mice control Mtb better than their WT counterparts, but also develop increased lung inflammation. Based on these findings, it was hypothesised that DCIR is a key regulator of the balance between type I and type II interferon responses, which is not only relevant in the context of TB, but in non-infectious inflammatory diseases. Currently, there are two billion people infected with TB worldwide, with 1.8 million people dying from TB every year. Additionally, TB is one of the leading causes of death in HIV positive patients globally. One of the major problems associated with this disease is that treatment for TB requires an intense and prolonged course of antibiotics that is highly dependent upon strict compliance by the patient. This can be quite difficult when a typical treatment consists of several antibiotics taken every day for up to 6 months, with no guarantee of complete clearance of the disease. Additionally, the persistence of TB can be attributed to a number of factors, one of which is its growing resistance to these antibiotics. Therefore, the development of novel strategies to treat this devastating disease are required. The revised aim of this project is to investigate the ligand of human DCIR and a murine homolog, mDCIR1, in order to better understand the function(s) of this receptor. At the conclusion of this project, the ligand for DCIR, both in human and mouse, has been identified and the biological significance of this interaction is currently being investigated.

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

Цел на проекта

Tuberculosis (TB), caused by the infectious agent Mycobacterium tuberculosis (Mtb), is a devastating disease and one of the leading causes of death in the developing world. Dendritic cells (DCs) play a key role in anti-mycobacterial immunity and express a range of pattern-recognition receptors which are involved in the recognition of Mtb antigens. Dr Olivier Neyrolles’ lab has characterised a number of these receptors, with the most recent being, and the focus of this project, the Dendritic Cell Immunoreceptor (DCIR). They have demonstrated that compared to wild-type mice, mice with a knockout in the DCIR homolog (mDCIR1) display increased antimycobacterial immunity as a result of an impaired response to type I interferon and an increased production of IL-12 in DCs. Consequently, mDCIR1-KO mice control Mtb better than their wild-type counterparts, but also develop increased lung inflammation. Based on these findings, it is hypothesised that DCIR is a key regulator of the balance between type I and type II interferon responses. The aim of this project is to implement a multidisciplinary strategy to investigate i) expression and function, ii) signalling, and iii) trafficking of DCIR in the context of Mtb infection. These studies will be focused on the aforementioned mDcir1 in addition to a second murine DCIR homolog mDCIR2, to evaluate the extent to which they play redundant or complementary roles in Mtb immunity. This will be accomplished using i) mDcir1- and mDcir2- KO mice to assess bacterial burden and the subsequent inflammatory response, ii) large-scale phosphoproteomics and transcriptomics to assess signalling events associated with DCIR-ligand binding, and iii) immunoelectron and immunofluorescence microscopy to examine the trafficking of the DCIR-ligand complex. This research will form a fundamental basis for the future exploitation of DCIR as an immunomodulatory checkpoint for the design of novel therapeutics aimed at reducing lung inflammation.

Оригинален текст от CORDIS (на английски).

Участници

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