HEИндивидуална стипендия2022–2024

MacroRhino · Deciphering rhinovirus-mediated macrophages impairment through the establishment of human induced pluripotent stem cells-derived macrophages

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

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 195 915 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Риновирусите (причината за настинката) могат да „парализират“ макрофагите – клетки, които почистват бактериите от организма. Разбирането на този механизъм помага при търсенето на начини за ограничаване на инфекциите и свързаните с тях заболявания.

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 rhinovirus-mediated macrophages impairment through the establishment of human induced pluripotent stem cells-derived macrophages

A growing body of evidence suggests that viruses can modulate myeloid cell responses, leading to long-term impairment of monocyte and macrophage phenotypes. While the long-term effects of viruses directly infecting macrophages on their function and phenotype have been well-studied, the impact of viruses that primarily infect other cell types on macrophages has been largely overlooked. However, recent data indicate that virus-induced modulation of macrophages can occur even in the absence of viral replication within these cells. In fact, viruses possess broader mechanisms for influencing innate immune responses beyond those observed in permissive cells. Understanding the strategies employed by viruses to modulate macrophage responses could not only reveal potential therapeutic targets to eliminate infections but also provide avenues to prevent or mitigate virus-associated pathologies. Human rhinovirus (HRV) has been shown to impair macrophage responses following secondary bacterial challenges. The host laboratory identified arpin as a key factor targeted by HRV, altering the phagocytic activity of macrophages, and demonstrated that HRV16-treated macrophages exhibit a "paralyzed" phenotype in terms of cytokine secretion. However, the precise mechanisms underlying the reprogramming of macrophages remain unclear. Additionally, it is not yet known whether HRV must replicate within macrophages to induce changes in their phenotype and function. Thus, my objectives are to determine (i) whether HRV can replicate in alveolar macrophages, and (ii) to elucidate the HRV-mediated mechanisms that lead to impaired macrophage function. Furthermore, while existing models used to study macrophages have certain advantages, they fail to fully replicate organ physiology, which plays a crucial role in shaping the phenotype of resident macrophages. To address this, I will develop a human lung alveolar macrophage-like cell (LAML) model derived from human induced pluripotent stem cells (h-iPSCs) to explore the aforementioned objectives.

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

Цел на проекта

A growing body of evidence suggest that viruses can modulate myeloid cells responses leading to long term impairment of monocytes/macrophages phenotypes. Whereas for virus directly infecting macrophages, the long-term effects on these cells function and phenotype have been extensively studied, for virus infecting other cell types, the effects on macrophages have been overlooked. Yet, recent data suggest that virus-mediated modulation of macrophages can even occurred when the virus do not replicate in these cells. Indeed, viruses have broader ways to modulate the innate immune responses than the one identified in permissive cells. Understanding the mechanisms of action employed by viruses to modulate macrophages responses could not only provide possible targets to eliminate the infection, but also offer therapeutic options to prevent/avoid virus-associated pathogenesis.Human rhinovirus (HRV) impairs macrophages’ responses upon secondary challenge with bacteria. The host laboratory identified arpin as a critical factor targeted by HRV to alter the phagocytic activity of macrophages and showed that HRV16-treated macrophages present a “paralysed” phenotype in terms of cytokine secretion. The precise mechanisms governing the reprogramming of the macrophages are however not fully elucidated. Furthermore, it is still unclear whether HRV needs to replicate within macrophages to reprogram their phenotype and functions. Therefore, my objectives are to decipher (i) if HRV can replicate in alveolar macrophages and (ii) what are the HRV-mediated mechanisms leading to impaired macrophages’ functions.Moreover, the models employed to study macrophages present advantages but do not recapitulate organ physiology, which plays a key role on the resident macrophage phenotype. Therefore, I will develop a model of human lung alveolar macrophage-like cell (LAML) derived from induced pluripotent stem cells (h-iPSC) to answer the above-mentioned objectives.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITE PARIS CITE · ParisКоординаторФранция