EuroPneumo Special Issue / pneumonia 2015 Oct 21;7:I–72


IL-22 contributes to recovery from pneumococcal pneumonia by

reducing collagen deposition in lung

Neil Ritchie, Tom Evans

University of Glasgow, Glasgow, UK

Pneumococcal pneumonia can cause dense pulmonary consolidation, which usually resolves within a few weeks of

treatment. IL-22 has been implicated in contributing to the resolution of pulmonary inflammation without fibrosis. We

explored the role of IL-22 in resolution of treated pneumococcal pneumonia in a murine model. IL22KO and wild-type

mice were infected intra-nasally with 3 x 10 6 cfu of serotype 3 Streptococcus pneumoniae. Infection was terminated

by administration of ceftriaxone once mice showed clinical signs of infection and again the following day. Lungs were

examined histologically and using a soluble collagen assay. Untreated mice developed severe pulmonary consolidation

with lung abscess formation and development of empyema. There was no significant difference in outcome between

IL-22KO mice and wild-type in outcome of untreated infection with similar histopathological changes and bacterial

burden. Treated mice resolved clinical illness and regained lost weight. Histological examination revealed improvement

in alveolar infiltration in both mouse types but IL-22KO mice had increased areas of sub-pleural collagen deposition

and lungs from IL-22KO mice had increased total collagen content. Treatment of pneumococcal pneumonia leads to

resolution of consolidation with relatively little pulmonary fibrosis. IL-22 was required for complete resolution and could

represent a novel therapeutic target to augment antibiotic treatment in severe pneumonia.


Pneumococcal colonisation and invasive disease studied in the porcine


Astrid de Greeff 1 , Saskia van Selm 2, 3 , Herma Buys 1 , Jose Harders-Westerveen 1 , Rahajeng

Tunjungputri 4 , Quirijn de Mast 4 , Andre van der Ven 4 , Norbert Stockhofe-Zurwieden 1 , Marien de

Jonge 2, 3 , Hilde Smith 1


Central Veterinary Institute, part of Wageningen UR, Lelystad, The Netherlands; 2 Laboratory of Pediatric Infectious Diseases, Department of

Pediatrics and Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The

Netherlands; 3 Raboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands, 4 Department of Internal Medicine, Nijmegen, The


Streptococcus pneumoniae is carried in the nasopharynx and spread by human-to-human transmission causing mild

diseases such as otitis media and sinusitis as well as severe diseases including pneumonia, meningitis, and sepsis.

Furthermore, S. pneumoniae is an important cause of septic arthritis, and endocarditis. Asymptomatic colonisation of

the nasopharynx is an essential precursor for pneumococcal disease. Piglets are the natural host for Streptococcus suis

infections. There are striking similarities between S. suis pathogenesis in piglets and S. pneumoniae pathogenesis in

humans. Piglets develop severe disease like meningitis, sepsis, arthritis, endocarditis or pneumonia upon infection with

S. suis. S. suis is carried in the oropharynx, the bacterium colonises the tonsil of piglets, similar to S. pneumoniae in

children. Furthermore, genetically S. suis and S. pneumoniae are closely related. Because pigs are very similar to humans

in terms of anatomy, genetics and physiology, we investigated the use of piglets as a model for human colonisation

and for the induction of pneumococcal invasive disease. Piglets inoculated intravenously with S. pneumoniae showed

persistent bacteraemia, frequently followed by arthritis. Moreover, in piglets inoculated intra-nasally the oropharynx

was colonised with S. pneumoniae for at least 7 consecutive days. This demonstrates that central aspects of human

pneumococcal infections also occur in the porcine model, and advocates the use of piglets in future colonisation,

transmission, and intervention studies. There is growing evidence that S. pneumoniae infections are associated with an

increased risk for cardiovascular events and stroke. Since the porcine and human cardiovascular systems are very similar,

the porcine pneumococcal model can be used to gain insight into the pathogenesis of this serious health problem.

pneumonia 2015 Volume 7


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