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Differential Pathological and Immune Responses in Newly Weaned Ferrets are associated with Mild Clinical Outcome of Pandemic 2009 H1N1 Infection

tetano

Editor, Senior Moderator
J Virol. 2012 Oct 10. [Epub ahead of print]
Differential Pathological and Immune Responses in Newly Weaned Ferrets are associated with Mild Clinical Outcome of Pandemic 2009 H1N1 Infection.
Huang SS, Banner D, Degousee N, Leon AJ, Xu L, Paquette SG, Kanagasabai T, Fang Y, Rubino S, Rubin B, Kelvin DJ, Kelvin AA.
Source

Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Abstract

Young children are typically considered a high risk group for disease associated with influenza infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss in comparison to adult ferrets, which paralleled the mild clinical symptoms in the younger age humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of young age group during H1N1pdm infection. We found that interferon and regulatory IL-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs, as well, numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed H1N1pdm infection triggered formation lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALT) in young ferrets which were associated with high levels of homeostatic chemokines, CCL19 and CXCL13, not seen in the adult ferrets with severe disease. These results may be extrapolated to a mild disease model seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective intervention and vaccination strategies against respiratory viruses.

PMID:
23055557
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23055557
 
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