Lung Infection and Innate Immunity
Received his PhD degree in 1992 from the University of Lille. Between 1986 and 1994, he studied helminth and protozoan parasites with the aim to improve vaccine efficacy (1986-1992) and to better understand mechanisms leading to drug resistance (1992-1994). He did a post-doc between 1992 and 1994 at the Walter and ELIZA Hall Institute, Royal Melbourne Hospital. In 1995, he obtained a tenure position at CNRS and he started to develop his own group in France, at the Institut Pasteur de Lille. Since 1995, François Trottein has been working on host/pathogen (parasites, bacteria, viruses) interactions; the objectives being to better understand escape mechanisms to immune responses and to exploit the innate immune system for designing novel therapeutic approaches. He has made major contribution in the field of innate immunity and lipids, either eicosanoids and antigenic lipids. For the later, he described the role (either beneficial or deleterious) of Natural Killer T cells, a population of lipid-reactive T cells, during infection. Since 2010, his group is developing research projects on influenza A virus and Streptococcus pneumoniae, the leading cause of bacterial pneumonia in humans.
Despite the application of vaccination programs, antibiotics and antiviral drugs, respiratory viral and bacterial infections are responsible for widespread morbidity and mortality. Co-morbidities, including lung diseases or obesity, can exacerbate the outcome of respiratory infections. For instance, severe bacterial infections are commonly associated with influenza or chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, and are significant contributors to the excess morbidity and mortality. Today’s treatments of secondary bacterial (pneumococcal) infections are still not effective enough and antibiotic resistance is a major issue. Hence, there is an urgent need for novel therapies. The general objective of the “Lung Infection and Innate Immunity” team is:
(1) To identify early host antibacterial and antiviral defense mechanisms during viral and bacterial infections,
(2) To define host molecular and cellular factors that predispose to bacterial infection during influenza infection, chronic obstructive pulmonary disease and obesity and,
(3) To develop new strategies to strengthen host defense mechanisms against respiratory pathogens.
Over the last few years, we have identified several targets that may be manipulated to control respiratory bacterial infections in the context of pre-existing pulmonary inflammation. Among them, factors able to control the Th17/Th22 axis may have therapeutic potentials. Innate stimulators, including agonists of the Toll-like receptor 5 (TLR5) and of Natural Killer T (NKT) cells are also promising candidates, particularly in combination with antibiotics. We are presently trying to optimize interventional procedures in experimental models to strengthen host defense mechanisms and to reinforce lung barrier functions. In parallel, we are developing clinical studies (collaboration with the CHRU Lille) to translate the findings in the human setting. Finally, non-biased strategies are being developed to identify other target candidates that might be ultimately exploited for the sake of patients. For instance, a focus is placed on the gut/lung axis and on the dysregulation of host and microbiota metabolism. Our recent data indicate a link between dysregulated gut homeostasis, metabolism and host defenses against respiratory bacterial intruders. We are trying to decipher these intricate and puzzling pathways with the hope of identifying novel diagnostic/prognostic markers and therapeutic candidates.