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Institut Pasteur Transverse Research Programs: HKU-Pasteur To Work On

The Relationship Between Stem Cells And Infectious Diseases

Flu is a contagious infectious disease caused by the influenza virus. Influenza A and B viruses circulate and cause seasonal epidemics. Each year about 3-5 million individuals develop a severe illness, causing 290 000 to 600 000 deaths. Flu is an infection of the respiratory tract characterized by a sudden onset of symptoms such as fever, cough, headache, muscle and joint pain. Most people recover within a week, but influenza can cause severe illness or death especially in high risk population, such as pregnant women, elderly, young children, individual with chronic diseases and health care workers.

Decline of independence after hospitalization has been reported in the elderly, as well as in specialized residence. This poses a number of issues, including an ever-increasing cost of national health care budgets. So far, researchers are mainly focused on respiratory complications leading to death, but few studies are addressing the causes and the consequences of the associated symptoms.

Between 2015 and 2018, Barbara Gayraud-Morel, from the unit of Stem Cells and Development (Institut Pasteur Paris) directed by Shahragim Tajbakhsh, had the opportunity to establish a fruitful collaboration with HKU-Pasteur, laying the foundations for this project under the Institut Pasteur Transverse Research Programs.

This partnership will unite their expertise on skeletal muscle research, stem cell biology and infectious diseases to investigate the consequences of influenza viral infection at a site where the biology of tissue stem cells has been investigated, notably in skeletal muscles. The observation that inflammatory molecules reach skeletal muscles led them to investigate the stem cell or pathogen driven systemic inflammation interactions which has so far remained unexplored. The compelling preliminary data gathered by the team led them to find that skeletal muscle stem cells respond to the systemic inflammation when there is an intranasal infection by the influenza virus. This opens a new field of research that exposes physiological response of tissues and organs to pathogens.

The characterisation of the molecular basis and functionality of this phenomenon will have a significant impact on human health by revealing an appreciated role of stem cells in symptoms associated with systemic inflammation during and after infection. This new field of investigation will inevitably be extended to other tissues and organs, for example, to evaluate if nerve, skin or intestinal stem cells are affected by systemic inflammation and result in altered function. With this new project, the team aims to understand the signalling molecules and mechanisms acting on muscle stem cells remotely from the site of infection, through the characterization of the biological response adopted by the muscle stem cells in this context of viral inflammation.

They will also explore if their observations on muscle stem cells in influenza-mediated inflammation could be a landmark of a more general stem cell response to acute inflammation in other contexts. To this end, this project associates the Centre for Translational Science Unit of Fabrice Chrétien (Institut Pasteur Paris), which has the expertise in another distinct systemic infection model, sepsis, in order to explore and compare the two paradigms, one related to viral response, and the other, a polybacterial infection.

This project, which is the result of synergistic expertise within the Pasteur network, opens a new field of investigation on the relationship between stem cells and infectious diseases. Strong preliminary data have paved the way for us to explore this area further and position this topic at the forefront of international research.


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