Antibiotics have revolutionized modern medicine but antibiotic resistance is an increasing threat to health, compromising the ability to treat bacterial infections and to carry out medical procedures, including chemotherapy, transplants, and surgery. The National, and International action plans demonstrate the necessity to develop innovative research to stop the progression of resistance in community-acquired and care-related bacterial infections. Antibiotics are uniquely considered as direct antimicrobial agents, and most efficacy evaluations are based on in vitro assays or immunosuppressed animals. However, there are several pieces of evidence that host immunity contributes to the efficacy of the antibiotic treatment. Thus, antibiotics by reducing the amount of the pathogenic bacteria, by modifying their virulence factors, and by killing/inactivating bacteria likely regulate the antibacterial immune responses. Deciphering the nature of cellular and molecular immune effectors contributing to antibiotic activity will open avenues to innovative approaches to combat infections with multidrug-resistant bacteria.
The team will promote two main research axes covering basic research to clinical research:
- Development of inhaled flagellin as an adjunct therapy in bacterial pneumonia
- Identification of immune correlates of protection throughout the differentiation and function of myeloid cells in the context of antibiotic treatment of bacterial infections
Jean-Claude Sirard received his PhD degree in 1995 from the University of Paris and the Pasteur Institute. Between 1991 and 1998, he studied bacterial pathogenesis of Bacillus anthracis, the causative agent of anthrax. He trained as a postdoctoral fellow between 1998 and 2003 at the Swiss Experimental Research Center on Cancer (ISREC) in Lausanne working on the interaction of intestinal epithelial cells with bacterial pathogens such as Salmonella enterica. He has been a pioneer in identifying flagellin as a major bacterial component that triggers pro-inflammatory responses in mammals. In 2003, he joined the Institut Pasteur de Lille as a laureate of the Young Investigator program ATIPE/AVENIR and he obtained a tenure position at Inserm to develop a research on epithelial innate immunity. The team led by Jean-Claude Sirard investigates the role of immune cells and immune mediators in host defense during respiratory infections by pathogenic bacteria, especially antibiotic-resistant Streptococcus pneumoniae and Klebsiella pneumoniae. The team aims at developing new adjuvants to trigger respiratory innate immunity in prophylaxis and therapeutic settings.