Host-Pathogen Interactions

Lower respiratory tract infections (LRTI) caused by virus (Influenza A virus, respiratory syncytial virus) or bacteria (Mycobacterium tuberculosis, Streptococcus pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae) are one of the major causes of morbidity and mortality worldwide. In the context of the current pandemic by SARS-CoV-2, polymicrobial LRTI are even more devastating and require further attention because additive and/or synergistic effects by several of these pathogens can exacerbate the severity of the pneumonia processes. Moreover, the wide use of antibiotics to avoid co-infections in COVID-19 patients worsens the already previously existing antimicrobial resistance (AMR) crisis. AMR consequences are, among others, increased hospitalization and lethality rates, changes in empirical therapeutical regimens, and development/transmission of new AMR mechanisms, together leading to increased economic burden and the urgent need to improve infection control measures.

AMR and therapeutic failure move us away from ensuring healthy lives and wellbeing, thus motivating this proposal. Numerous international programs investigate and monitor the prevalence of AMR pathogens in hospitals but are mostly observational and lack fundamental studies designed to provide mechanisms explaining the changes in epidemiology, virulence, and resistance in a pandemic context. PERCLINRESP aims to deeply expand our understanding of the host-pathogen interplay within the human airways, developing and validating a whole range of innovative prophylactic, diagnostic, prognostic and therapeutic measures for improved clinical management of LRTI within a personalized framework.

Key specific challenges identified in this project are: the need to understand specific host responses to airway infection (with focus on human genetics, trained immunity and host soluble factors); the need to elucidate patterns of (poly)microbial infection dynamics; the need for novel, alternative and complementary infection models of disease; and the need for increased drug efficacy and sustainability. A multidisciplinary collaborative work plan is proposed to tackle these challenges. Specific aims are: 1) Elucidating mono- and polymicrobial infection dynamics in acute and chronic LRTI; 2) Characterisation of molecular mechanisms underlying the hostpathogen interplay; 3) Search for novel diagnostic and prognostic biomarkers with a focus on disease susceptibility and severity; 4) Development of preventive tools based on trained immunity and immunoregulatory properties; 5) Development of improved antibacterial therapeutics. PERCLINRESP overall aim is to provide useful solutions translated to all range of end-users.

PERCLINRESP expected outcomes are i) Innovative personalized diagnosis, prognosis, prevention, surveillance and treatment of LRTI; ii) (Inter)national results dissemination; iii) Diffusion to health authorities, patient associations, society in general; iv) Industrial cooperation; vi) Research training.