title: Critical Role of IL-22/IL22-RA1 Signaling in Pneumococcal Pneumonia.
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.
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224.
authors.forename: Giraldina
authors.initials: G
authors.lastname: Trevejo-Nunez
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224.
authors.forename: Waleed
authors.initials: W
authors.lastname: Elsegeiny
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224.
authors.forename: Parker
authors.initials: P
authors.lastname: Conboy
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224.
authors.forename: Kong
authors.identifier: 0000-0001-6980-5454
authors.initials: K
authors.lastname: Chen
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224 jay.kolls@chp.edu.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: D000818:Animals; D058491:Bacterial Load; D003176:Complement C3 / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000008:administration & dosage / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity; D000097043:Interleukin-22
chemical_list: D003176:Complement C3; D016207:Cytokines; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor