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C-type lectin receptors and their implication in the innate response against respiratory pathogens

English title C-type lectin receptors and their implication in the innate response against respiratory pathogens
Applicant Fernandez Gonzalez Santiago
Number 204636
Funding scheme Project funding
Research institution Istituto di ricerca in biomedicina (IRB) Facoltà di scienze biomedice
Institution of higher education Università della Svizzera italiana - USI
Main discipline Immunology, Immunopathology
Start/End 01.05.2022 - 30.04.2026
Approved amount 908'000.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Medical Microbiology

Keywords (7)

Viral immunopathology; Lung infection; Inflammation; Viral recognition; Innate immune response; Respiratory diseases; glycobiology

Lay Summary (Italian)

Lead
È noto che i patogeni respiratori diano origine a periodici focolai di pandemia. L'infezione causata da questi agenti patogeni è caratterizzata da uno stadio altamente infiammatorio a cui, in molti casi, segue un collasso dell'apparato respiratorio, causando gravi danni o addirittura la morte del paziente infetto. Nonostante la sua importanza, ci sono ancora molte incognite sull'inizio della risposta infiammatoria contro il virus.
Lay summary

Precedenti studi realizzati dal nostro team di ricerca hanno identificato un gruppo di recettori di membrana responsabili del riconoscimento del virus dell'influenza e dell'inizio della risposta infiammatoria nelle vie aeree. In questo progetto continueremo a caratterizzare questi recettori e le risposte contro altri virus respiratori, come il coronavirus e contro i batteri respiratori come lo pneumococco. Inoltre, progetteremo e testeremo diverse terapie volte a promuovere o inibire la risposta infiammatoria nel corso di un'infezione o durante la vaccinazione. Tra le diverse tecnologie possibili, utilizzeremo la Nobel nanocarrier per sviluppare nuovi trattamenti che aiuteranno nel controllo dell’infiammazione. Per raggiungere questo obiettivo lavoreremo in stretta collaborazione con partner internazionali e esperti mondiali nel campo delle malattie infettive e della farmacologia. Inoltre, forniremo un'eccellente formazione a tre ricercatori nel campo delle malattie infettive e della farmacologia.

Direct link to Lay Summary Last update: 18.03.2022

Responsible applicant and co-applicants

Employees

Name Institute

Associated projects

Number Title Start Funding scheme
189699 IMMUNEMAP: Enabling data-driven immunological research by making two-photon intravital microscopy data FAIR 01.12.2019 Biolink funds
176124 Role of lymph node phagocytes in the regulation of the IgG-mediated suppression of the immune response to influenza vaccine 01.10.2017 Project funding

Abstract

Respiratory pathogens are known for giving rise to periodic pandemic outbreaks. The innate immune system senses these pathogens via different receptors, among which, the C-type lectin receptors recognize specific pathogen-associated carbohydrates. Previous studies have demonstrated that one of these receptors, SIGN-R1, has exquisite pathogen-recognition capacities, detecting not only viruses, but also bacteria and fungi. In addition, SIGN-R1 plays a crucial role in the activation of the initial inflammatory response, which is instrumental in the pathogenesis of these diseases.Therefore, the main goal of this project is to study how the C-type lectin-mediated inflammatory response initiated against the respiratory pathogens influenza, Streptococcus pneumoniae (Objective 1) and SARS- CoV-2 (Objective 2), affect the outcome of the disease. In addition, we will investigate new approaches aimed at using C-type lectins as therapeutic targets (Objective 3). Amongst them, we will develop SIGN- R1 chimeric molecules, such as SIGN-R1-C3d or SIGN-R1-Fc, intended to opsonize the pathogen and direct it towards a specific type of immune cells. Moreover, we will design and evaluate different therapies intended to promote or inhibit the SIGN-R1-mediated inflammatory response in the course of an infection or during vaccination. Finally, we will also develop nanocarriers specifically targeted towards SIGN-R1- expressing cells.In the last five years, our group has published a series of papers characterizing the innate response to respiratory pathogens. During these studies we have developed a unique toolbox of in vivo and in vitro microscopy techniques, including intravital 2-photon microscopy, as well as other immunology and microbiology-based methods that will be used in this project. Additionally, we will take advantage of our network of international experts in pharmacology and molecular biology to design the new compounds with a potential therapeutic use against influenza, S. pneumoniae and SARS-CoV-2. The successful completion of this project will provide significant benefits to the fields of vaccinology and infectious diseases, especially regarding the modification of the inflammatory and humoral responses against a specific antigen as well as the neutralization of the pathogen. Moreover, our results will be valuable to understand the role of the early inflammatory process in the immune cell-pathogen dynamics in other major respiratory diseases.
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