期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 177, 期 2, 页码 208-218出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.200612-1890OC
关键词
respiratory syncytial virus; interferon-gamma; asthma; airway hyperresponsiveness; mice
资金
- NHLBI NIH HHS [L30 HL154180, HL-36577, HL-61005] Funding Source: Medline
- NICHD NIH HHS [HD053557, R01 HD053557-01A2, R01 HD053557] Funding Source: Medline
Rationale. Severe respiratory syncytial virus (RSV) bronchiolitis has been associated with deficient IFN-gamma production in humans, but the role of this cytokine in determining the outcome of reinfection is unknown. Objectives: To define the role of IFN-gamma in the development of RSV-mediated airway hype rresponsiveness (AHR) and lung histopathology in mice. Methods: Wild-type (WT) and IFN-gamma knockout mice were infected with RSV in the newborn or weaning stages and reinfected 5 weeks later. Airway responses were assessed on Day 6 after the primary or secondary infection. Measurements and Main Results: Both WT and IFN-gamma knockout mice developed similar levels of AHR and airway inflammation after primary infection. After reinfection, IFN-gamma knockout mice, but not WT mice, developed AHR, airway eosinophilia, and mucus hyperproduction. Intranasal administration of IFN-gamma during primary infection but not during reinfection prevented the development of these altered airway responses on reinfection in IFN-gamma knockout mice. Adoptive transfer of WT T cells into IFN-gamma knockout mice before primary infection restored IFN-gamma production in the lungs and prevented the development of altered airway responses on reinfection. Treatment of mice with IFN-gamma during primary neonatal infection prevented the enhancement of AHR and the development of airway eosinophilia and mucus hyperproduction on reinfection. Conclusions: IFN-gamma production during primary RSV infection is critical to the development of protection against AHR and lung histopathology on reinfection. Provision of IFN-gamma during primary infection in infancy may be a potential therapeutic approach to alter the course of RSV-mediated long-term sequelae.
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