Understanding respiratory tract infections through minimally-invasive, daily nasal sampling in children

Descripción del proyecto

Infección, interacciones hospedador-patógeno y transmisión de las infecciones respiratorias

La neumonía es una infección potencialmente grave que afecta a los pulmones y que puede estar causada por diferentes microorganismos patógenos, como bacterias y virus. Sin embargo, algunos microorganismos responsables de la neumonía pueden colonizar las vías respiratorias altas sin causar infección. Aún no se conoce del todo el papel de estos microorganismos en la transmisión comunitaria y la inmunidad. En el proyecto DailySAM, financiado por el Consejo Europeo de Investigación, se pretende cerrar esta brecha del conocimiento investigando las infecciones de las vías respiratorias altas en niños. Sus investigadores optimizarán las técnicas de muestreo nasal con tiras de matriz absorbente sintética y obtendrán datos sobre el microbioma y las respuestas inmunitarias del hospedador. En último término, se prevé que los resultados del proyecto no solo guíen el desarrollo de nuevos diagnósticos y tratamientos, sino que además mejoren la comprensión sobre cómo se propagan los microorganismos patógenos.

Objetivo

Pneumonia is the number one infectious cause of death in children worldwide. Many of the viruses and bacteria that cause pneumonia regularly infect, or colonize, the upper respiratory tract (URT) without causing disease. This drives community transmission but is also an important source of immunity. The processes and key host immune and microbiota factors that determine the infection kinetics, transmission and development of immunity during such infections need elucidation.

I have recently optimized minimally-invasive nasal sampling analysis methods using Synthetic Absorptive Matrix (SAM) strips that now allow me to address these knowledge gaps. Through the daily collection of such well-tolerated nasal samples in children, I will study non-pathological, naturally-acquired URT infections, but also controlled infections in an ethical and safe manner using the live attenuated influenza vaccine. In addition, I will perform high frequency nasal sampling in groups of schoolchildren to precisely measure transmission events over time and even infer exposure. Incoming bacteria, viruses and the resident URT microbiome as well as mucosal host innate and adaptive immune responses will be quantified in parallel throughout infections using existing and new high-throughput assays, including an antigen array and microfluidic qPCR for 32 pathogens. Multi-omics integrative time-series analyses and mathematical modelling will be used to identify parameters that are central and predictive for pathogen acquisition, replication and clearance; as well as for transmission and immune boosting. Key novel markers and concepts will be validated using state-of-the-art in vitro mucosal models.

The comprehensive and detailed understanding of URT infections obtained in this project can lead to better diagnostics, mucosal targeted therapies and vaccines, and provide a basis for the improved predictions of pathogen spread and public health effects of interventions at the population level.