Clara cell secretory protein modulates lung inflammatory and immune responses to respiratory syncytial virus infection.
Clara cell secretory protein (CCSP) has been shown to have anti-inflammatory and immunomodulatory functions in the lung. Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants and young children. RSV usually infects small airways and likely interacts with the Clara cells of bronchioles. To determine a possible role for CCSP during acute RSV infection, CCSP-deficient (CCSP(-/-)) and wild-type (WT) mice were intratracheally infected with RSV and the lung inflammatory and immune responses to RSV infection were assessed. RSV-F gene expression was increased in the lungs of CCSP(-/-) mice as compared with WT mice following RSV infection, consistent with increased viral persistence. Lung inflammation was significantly increased in CCSP(-/-) mice as compared with WT mice after infection. Moreover, although the levels of Th1 cytokines were similar, the levels of Th2 cytokines and neutrophil chemokines were increased in the lungs of CCSP(-/-) mice following infection. Physiologic endpoints of exacerbated lung disease, specifically airway reactivity and mucus production, were increased in CCSP(-/-) mice after RSV infection. Importantly, restoration of CCSP in the airways of CCSP(-/-) mice abrogated the increased viral persistence, lung inflammation, and airway reactivity. These findings suggest a role for CCSP and Clara cells in regulating lung inflammatory and immune responses to RSV infection.
Wang
Shan-Ze
SZ
Asthma and Pulmonary Immunology Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
Rosenberger
Cynthia L
CL
Bao
Yi-Xiao
YX
Stark
James M
JM
Harrod
Kevin S
KS
D000403:Airway Resistance / Q000235:genetics / Q000276:immunology; D000423:Alcian Blue; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D008171:Lung Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D009088:Mucoproteins / Q000032:analysis / Q000096:biosynthesis; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010503:Periodic Acid-Schiff Reaction; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014598:Uteroglobin; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D009088:Mucoproteins; D011506:Proteins; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin; D000423:Alcian Blue