Project description
Mechanisms of virus-mediated macrophage response modulation
Viruses modulate myeloid cell responses, impairing macrophage phenotypes, and recent data suggest that this impairment can occur even without virus replication in these cells. Human rhinovirus (HRV) impairs macrophages’ responses to bacterial infection via downregulation of cytokine secretion. Understanding the mechanisms employed by viruses to modulate macrophages’ responses could offer therapeutic options to prevent virus-associated pathogenesis. Funded by the Marie Skłodowska-Curie Actions programme, the MacroRhino project aims to discover if HRV can replicate in alveolar macrophages and elucidate the HRV-mediated mechanisms of macrophage impairment. The researchers will develop a novel model of human lung alveolar macrophage-like cells derived from induced pluripotent stem cells to recapitulate organ physiology and the resident macrophage phenotype.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences microbiology virology
- medical and health sciences basic medicine physiology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2021-PF-01
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75006 PARIS
France
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