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T6 The role of IL-17A in a mouse model of pulmonary infection caused by streptococcus pneumoniae is strain dependent
  1. ND Ritchie1,
  2. TJ Mitchell2,
  3. TJ Evans1
  1. 1University of Glasgow, Glasgow, United Kingdom
  2. 2University of Birmingham, Birmingham, United Kingdom


Background The cytokines interleukin 17A and interleukin 22 are known to be important in host defence against Gram-negative infection. However, their role in the innate immune response to pneumococci remains poorly understood. We aimed to investigate the role of these cytokines in an animal model of pneumococcal infection.

Methods Wild type (WT), IL-17 receptor A-/- (IL17RAKO) and IL-22-/- C57Bl/6 mice were infected intranasally with serotype 4 (TIGR4) and serotype 3 (SRL1) pneumococci. Neutrophils for in vitro experiments were obtained by peritoneal lavage following injection of casein.

Results TIGR4 was cleared from the lungs of mice within 48 hours but invaded early in the course of the infection causing bacteraemia and disseminated infection. In contrast, SRL1 invaded into blood late in the course of infection but caused a dense consolidative pneumonia with purulent empyema. IL-17A and IL-22 were detected in alveolar lavage within 6 hours of infection but fell in later infection suggesting an innate source. Contrasting results were obtained when knockout animals were infected. In TIGR4 infection, IL17RAKO were more susceptible to infection (P = 0.04) and this was due to an increased incidence of early bacteraemia in these animals. In contrast, following SRL1 infection in IL17RAKO animals, there was improved survival (P = 0.004). In both types of infection, IL22KO animals demonstrated an intermediate phenotype that did not reach statistical significance. IL17RAKO mice had decreased neutrophils in blood and lung within 24 hours of infection in keeping with the known biological actions of IL-17A. Studies using isolated cells showed that TIGR4 was phagocytosed and killed by neutrophils but uptake and killing of SRL1 was ineffective. Experiments with fluorescent bacteria confirmed poor neutrophil uptake of SRL1 relative to TIGR4. Depletion of WT mouse neutrophils with a monoclonal antibody demonstrated a trend towards delayed mortality and improved outcome in SRL1 infection.

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