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

• Published in: The Journal of immunology (1950) 2016-09, Vol.197 (5), p.1877-1883
• Main Authors: Trevejo-Nunez, Giraldina, Elsegeiny, Waleed, Conboy, Parker, Chen, Kong, Kolls, Jay K
• Format: Article
• Language: English
• Subjects: 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; Streptococcus pneumoniae - immunology; Streptococcus pneumoniae - pathogenicity
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1600528

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.