Treating the host in Dengue: mediators and pathways of resolution as a new therapeutic paradigm

治疗登革热宿主：介质和解决途径作为新的治疗范式

• 批准号: MR/N017544/1
• 负责人: Mauro Perretti
• 金额: $ 30.94万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN017544%2F1
• 关键词: Treating; host; Dengue; mediators; pathways

Dengue infects some 400 million people in 128 countries each year in poorest regions of the world, yet proper therapeutic treatment does not exist. According to the Brazilian Ministry of Health, significant dengue epidemics have occurred in the last 10 years in Brazil with around 1 million cases/year reported in the last 4 years (http://portalsaude.saude.gov.br/index.php/situacao-epidemiologica-dados-dengue). Only in May it was reported that several States of Brazil are experiencing a new epidemic (http://www.bbc.co.uk/news/world-latin-america-32589268). Although severe disease accounts for only approximately 2% of all reported cases, no specific treatment is available and it is not possible at present to define patients at risk to develop severe disease. The combination of high incidence and no specific therapeutic options places an enormous burden on already over-stretched health systems.In this proposal we intend to study the impact and roles of endogenous mediators that temper excessive inflammation and promote resolution on the dynamics of Dengue disease. To study profiles of expression, and how the levels of these protective mediators change over time, we will use cutting-edge analytical protocols (to be done in the UK). To study the relevance of these mediators to human disease, we will use patient samples as well as novel models in experimental animals (to be done in Brazil). The latter mirror several findings in patients and provide a crucial in vivo environment to underpin identification and the translation of novel therapies into humans. Our new approach proposes to investigate inflammatory processes during the infection of Dengue and, more novel, the impact that endogenous tissue-protective pathways may have on the course of infection (this area is often referred to as 'resolution of inflammation'). Therefore, with this project we seek funding to study new mechanisms and processes in Dengue with the dual aim:1. Discover novel mechanisms in Dengue using human samples and animal models.2. Provide proof-of-concept results that 'pushing' endogenous pathways of resolution can provide a novel therapeutic avenue for Dengue.The over-arching remit of this work is the novel notion that to combat excessive inflammation associated with infection we could treat the host, to deal with the infectious agents, thus keep them under control and favour their disposal.

项目成果

Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35.

• DOI: 10.1111/bph.15919
• 发表时间: 2022-10
• 期刊: British journal of pharmacology
• 影响因子: 7.3

Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease.

• DOI: 10.7554/elife.73853
• 发表时间: 2022-03-16
• 期刊: eLife
• 影响因子: 7.7
• 作者: Costa VV;Sugimoto MA;Hubner J;Bonilha CS;Queiroz-Junior CM;Gonçalves-Pereira MH;Chen J;Gobbetti T;Libanio Rodrigues GO;Bambirra JL;Passos IB;Machado Lopes CE;Moreira TP;Bonjour K;Melo RCN;Oliveira MAP;Andrade MVM;Sousa LP;Souza DG;Santiago HDC;Perretti M;Teixeira MM
• 通讯作者: Teixeira MM