T helper 1 background protects against airway hyperresponsiveness and inflammation in guinea pigs with persistent respiratory syncytial virus infection.
A family history of allergy has been implicated in children who develop post-bronchiolitis wheezing and asthma. In a guinea pig model of respiratory syncytial virus (RSV) lung infection, we evaluated the role of host Th1 background (either genetic or induced) on the development of a persistent infection, nonspecific airway hyperresponsiveness (AHR) and airway inflammation. Allergy resistant/T helper 1 (Th1)-skewed strain 2 guinea pigs (STR2) and cytosine phosphate guanine oligodeoxynucleotides (CpG-ODN) (Th1 stimuli) pretreated Cam Hartley guinea pigs (CH) were inoculated with RSV and compared with virus-inoculated allergy-susceptible/Th2-skewed CHs and to sham-inoculated STR2 and CH, 60 d post-inoculation. We measured titers of intrapulmonary RSV, lung interferon (IFN)-gamma and interleukin (IL)-5 mRNA expression, AHR and airway T cells and eosinophils. All virus-inoculated groups of animals showed evidence of persistent RSV lung infection; however, Th2-skewed guinea pigs had virus-associated AHR and significantly greater levels of airway T cells and eosinophils. In conclusion, RSV can establish persistent infection of the guinea pig lung regardless of host Th1/Th2 background; however; a host Th1 background limits the extent of virus-associated AHR and airway inflammation. Heterogeneity in virus-host interactions may be relevant to understanding why some children hospitalized for RSV bronchiolitis go on to develop recurrent wheezing/asthma symptoms.
Sutton
Troy C
TC
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada V6Z 1Y6.
Tayyari
Farnoosh
F
Khan
M Aatif
MA
Manson
Heather E
HE
Hegele
Richard G
RG
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001988:Bronchiolitis / Q000209:etiology / Q000821:virology; D002648:Child; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology*; D007372:Interferons / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D007372:Interferons