Critical Role of IL-22/IL22-RA1 Signaling in Pneumococcal Pneumonia

J Immunol. 2016 Sep 1;197(5):1877-83. doi: 10.4049/jimmunol.1600528. Epub 2016 Jul 25.

Abstract

IL-22-IL-22R signaling plays a crucial role in regulating host defenses against extracellular pathogens, particularly in the intestine, through the induction of antimicrobial peptides and chemotactic genes. However, the role of IL-22-IL-22R is understudied in Streptococcus pneumoniae lung infection, a prevalent pathogen of pneumonia. This paper presents the findings of IL-22 signaling during a murine model of pneumococcal pneumonia and improvement of bacterial burden upon IL-22 administration. IL-22 was rapidly induced in the lung during pneumococcal infection in wild-type mice, and Il22(-/-) mice had higher pneumococcal burdens compared with controls. Additionally, mice with hepatic-specific deletion of Il22ra1 also had higher bacterial burdens in lungs compared with littermate controls after intrapulmonary pneumococcal infection, suggesting that IL-22 signaling in the liver is important to control pneumococcal pneumonia. Thus, we hypothesized that enhancement of IL-22 signaling would control pneumococcal burden in lung tissues in an experimental pneumonia model. Administration of rIL-22 systemically to infected wild-type mice decreased bacterial burden in lung and liver at 24 h postinfection. Our in vitro studies also showed that mice treated with IL-22 had increased C3 expression in the liver compared with the isotype control group. Furthermore, serum from mice treated with IL-22 had improved opsonic capacity by increasing C3 binding on S. pneumoniae Taken together, endogenous IL-22 and hepatic IL-22R signaling play critical roles in controlling pneumococcal lung burden, and systemic IL-22 decreases bacterial burden in the lungs and peripheral organs by potentiating C3 opsonization on bacterial surfaces, through the increase of hepatic C3 expression.

MeSH terms

  • Animals
  • Bacterial Load
  • Complement C3 / genetics
  • Complement C3 / immunology
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Interleukin-22
  • Interleukins / administration & dosage
  • Interleukins / blood
  • Interleukins / immunology*
  • Interleukins / metabolism*
  • Liver / immunology
  • Liver / microbiology
  • Lung / immunology
  • Lung / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis
  • Pneumonia, Pneumococcal / immunology*
  • Pneumonia, Pneumococcal / metabolism*
  • Pneumonia, Pneumococcal / microbiology
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin / metabolism*
  • Signal Transduction*
  • Streptococcus pneumoniae / immunology
  • Streptococcus pneumoniae / pathogenicity

Substances

  • Complement C3
  • Cytokines
  • Interleukins
  • Receptors, Interleukin
  • interleukin-22 receptor