Abstract
Infection with respiratory syncytial virus (RSV) in neonatal mice leads to exacerbated disease if mice are reinfected with the same virus as adults. Both T cells and the host major histocompatibility complex genotype contribute to this phenomenon, but the part played by innate immunity has not been defined. Since macrophages and natural killer (NK) cells play key roles in regulating inflammation during RSV infection of adult mice, we studied the role of these cells in exacerbated inflammation following neonatal RSV sensitization/adult reinfection. Compared to mice undergoing primary infection as adults, neonatally sensitized mice showed enhanced airway fluid levels of interleukin-6 (IL-6), alpha interferon (IFN-α), CXCL1 (keratinocyte chemoattractant/KC), and tumor necrosis factor alpha (TNF-α) at 12 to 24 h after reinfection and IL-4, IL-5, IFN-γ, and CCL11 (eotaxin) at day 4 after reinfection. Weight loss during reinfection was accompanied by an initial influx of NK cells and granulocytes into the airways and lungs, followed by T cells. NK cell depletion during reinfection attenuated weight loss but did not alter T cell responses. Depletion of alveolar macrophages with inhaled clodronate liposomes reduced both NK and T cell numbers and attenuated weight loss. These findings indicate a hitherto unappreciated role for the innate immune response in governing the pathogenic recall responses to RSV infection.
Highlights
Most cases of infantile viral bronchiolitis are caused by respiratory syncytial virus (RSV) infection [1]
Mice that had initially been infected as neonates had significantly higher levels of IL-6 (P Ͻ 0.01; Fig. 1A), TNF-␣ (P Ͻ 0.01; Fig. 1B), and CXCL1/keratinocyte chemoattractant (P Ͻ 0.01; Fig. 1C) at 12 h and 24 h after reinfection than mice first infected as adults
We show that neonatal RSV infection primed for pathogenic innate and adaptive immune responses on RSV reinfection in adults
Summary
Most cases of infantile viral bronchiolitis are caused by respiratory syncytial virus (RSV) infection [1]. To investigate the long-term effects of viral lung infection in early life, we developed a mouse model of neonatal RSV infection followed by adult reinfection [5]. Both CD4 and CD8 T cells play a role in this phenomenon, as does the major histocompatibility complex (MHC) genotype [6, 7], but these factors may not fully explain the delayed effects of neonatal sensitization, since T cell depletion during secondary reinfection does not completely abrogate disease. Cells of the innate immune system play an important role in the long-term effects of neonatal RSV infection
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.