RESUMO
Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptides and is inhibited by the soluble decoy receptor IL-22-binding protein (IL-22BP). Little is known about the effect of the IL-22/IL-22BP regulatory pathway on lung infection, and it has not been studied in the setting of super-infection. We exposed wild-type and IL-22BP-/- mice to influenza A/PR/8/34 for 6 days prior to infection with S. aureus (USA300) S. pneumoniae. Super-infected IL-22BP-/- mice had decreased bacterial burden and improved survival compared to controls. IL-22BP-/- mice exhibited decreased inflammation, increased lipocalin 2 expression, and deletion of IL-22BP was associated with preserved epithelial barrier function with evidence of improved tight junction stability. Human bronchial epithelial cells treated with IL-22Fc showed evidence of improved tight junctions compared to untreated cells. This study revealed that IL-22BP-/- mice are protected during influenza, bacterial super-infection, suggesting that IL-22BP has a pro-inflammatory role and impairs epithelial barrier function likely through interaction with IL-22.
Assuntos
Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Proteínas de Transporte/metabolismo , Interleucinas/metabolismo , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/virologia , Superinfecção , Animais , Infecções Bacterianas/genética , Infecções Bacterianas/patologia , Carga Bacteriana , Barreira Alveolocapilar/metabolismo , Barreira Alveolocapilar/patologia , Barreira Alveolocapilar/virologia , Proteínas de Transporte/genética , Modelos Animais de Doenças , Expressão Gênica , Interleucinas/genética , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Knockout , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/patologia , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/patologia , Permeabilidade , Ligação Proteica , Staphylococcus aureus , Streptococcus pneumoniae , Junções Íntimas , Interleucina 22RESUMO
PURPOSE OF REVIEW: Cystic fibrosis (CF) has received a lot of attention in the past few years because of increased longevity and the emergence of ground-breaking new drugs targeting the molecular and cellular defects, making a huge clinical difference, and - not incidentally - carrying massive price tags. The prices of these new drugs make the question of overall costs of CF care highly relevant. RECENT FINDINGS: This article reviews recent developments in CF science and treatment, and highlights areas that contribute to costs of CF care, emphasizing how these costs have increased. SUMMARY: This article should help the pediatrician stay abreast of high points of CF care, with an awareness of the factors that wield the biggest influence on overall costs, to patients, families and the US healthcare system.
