Transregional Collaborative Research Center SFB-TR 84 - “Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia“

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EN1- Emmy Noether Junior Research Groups

Regulation of protective pulmonary immunity by innate pathways sensing bacterial viability

 

The immune system is faced with the delicate task of providing sufficient host protection while avoiding unnecessary inflammatory tissue damage. Thus, immune responses must be closely scaled to the infectious threat level posed by a given microbial encounter. We could recently demonstrate an inherent capacity of the immune system to sense bacterial viability, and hence infectivity. Immune cells discriminate live from dead bacteria through the detection of a novel class of ‘pathogen associated molecular patterns’ (PAMPs), called ‘viability associated PAMPs’ (vita-PAMPs). Bacterial messenger (m)RNA represent such a vita-PAMP, the detection of which signals bacterial life to the immune system and elicits robust immune responses, not warranted for dead bacteria.

In the current project we will investigate the role of the identified pathways for the generation of protective pulmonary immunity. Given the often-observed lifelong protective immunity conferred by live vaccines and survived infections, we will investigate the role of ‘viability-detection’ and the identified signaling pathways in pulmonary B cell responses; particularly in the production of pathogen-specific IgA and IgG. Notably, very little is known about the innate regulation of pulmonary antibody responses. In this project we aim to identify the microbial signals, the responding immune cells and the molecular pathways that control protective humoral immune responses in the lung. These studies will provide detailed insight into the mechanisms of pulmonary immunity, which is important for the development of novel mucosal vaccines strategies.