IL-1R signaling enables bystander cells to overcome bacterial blockade of host protein synthesis

• DOI: 10.1073/pnas.1501289112
• Publication Date: 2015-06-02T15:08:47Z
• Authors: Alan M. Copenhaver; Cierra N. Casson; Hieu T. Nguyen; Matthew M. Duda; Sunny Shin
• Keywords: Male; Mice, Knockout; Receptors, Interleukin-1 Type I; 0303 health sciences; Virulence; Tumor Necrosis Factor-alpha; Macrophages; Immunity, Innate; Legionella pneumophila; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Host-Pathogen Interactions; Animals; Cytokines; Female; B7-2 Antigen; Inflammation Mediators; Legionnaires' Disease; Interleukin-1; Signal Transduction

Significance

Pathogens use virulence factors to inhibit key immune cell functions and would be expected to impair immune responses to infection. However, immune responses are still generated against infection, suggesting that the immune system has evolved mechanisms for overcoming pathogenic activity. Here, we demonstrate that cells infected with Legionella pneumophila synthesize IL-1 despite a pathogen-imposed block in host translation, but are unable to produce other critical cytokines. IL-1 signaling allows uninfected bystander cells to produce protective cytokines. Our data thus demonstrate a key role for communication between infected and uninfected bystander cells in overcoming pathogenic activities. This mechanism of immune activation has broad significance for our understanding of how successful immune responses are generated against pathogens.