The trancriptional factor, Nrf2 is critical for the protection against pneumococcal pneumonia. (INM3P.400)

Abstract

Abstract Pneumonia is one of the major clinical complications of pneumococcal disease. Innate immunity provides an immediate response to S. pneumoniae that can be protective, but if not controlled, can also lead to deleterious inflammation, extensive tissue damage and mortality. A complete understanding of the regulation of innate immunity and attendant inflammatory responses are critical for clinical control of respiratory bacterial infections. To better comprehend this dynamic process during pneumococcal infection, we specifically focused on the transcriptional factor, Nrf2, which can be both induced by inflammation and critically regulates inflammatory responses. Of interest, acute lung injury (ALI) in humans is correlated with functional polymorphisms in the Nrf2 promoter region. Our studies showed that mice deficient in Nrf2 were highly susceptible to in vivo pneumococcal pneumonia. Nrf2 deficiency was associated with enhanced production of pro-inflammatory cytokines and infiltration of neutrophils into the lungs following infection. However, immunization with the polysaccharide conjugate vaccine completely protected both Nrf2-/- and Nrf2+/- mice against pneumococcal challenge. This study provides evidence that Nrf2 is critical for protection against pneumococcal pneumonia by suppressing deleterious inflammation. In addition, the results suggest that pneumococcal vaccination should be performed to protect humans who have an Nrf2-associated genetic predisposition to develop ALI <!--EndFragment-->