T Helper 1 Background Protects Against Airway Hyperresponsiveness and Inflammation in Guinea Pigs With Persistent Respiratory Syncytial Virus Infection

摘要

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)-γ 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.Abbreviations: ACh, acetylcholine; AHR, airway hyperresponsiveness; AOI, area of interest; CH, Cam Hartley guinea pigs; CpG-ODN, cytosine phosphate guanine oligodeoxynucleotides; OA, ovalbumin; PC2, provocative concentration of ACh associated with a doubling of baseline; pfu, plaque-forming units; RL, lung resistance; RSV, respiratory syncytial virus; STR2, strain 2 guinea pigs; Th1 (2), T helper 1 (2)