Plasmacytoid dendritic cell depletion leads to an enhanced mononuclear phagocyte response in lungs of mice with lethal influenza virus infection.

Plasmacytoid dendritic cells (pDCs) have been implicated both in the control and pathogenesis of influenza virus infection. We demonstrate that pDC depletion has marked effects on the response of mononuclear phagocytes, including conventional DCs (cDCs) and macrophages, to lethal influenza virus infection. Infection of mice lacking pDCs through antibody-mediated depletion resulted in substantially increased accumulation of mononuclear phagocytes and their progenitors in lungs compared to non-treated controls.

Adjuvants that stimulate TLR3 or NLPR3 pathways enhance the efficiency of influenza virus-like particle vaccines in aged mice.

There is intense interest in the design and use of vaccine strategies against influenza to enhance protective immune responses in the elderly. To address the need for improved influenza vaccines for the aged, two inflammatory adjuvants, Imject(®) alum (a stimulator of the Nod-like receptor, Nalp3) and poly I:C (a toll-like receptor type 3 ligand), were used during vaccination with novel influenza virus-like particles (VLP). Adult (4 month old) or aged (24 month old) mice were vaccinated with VLPs alone or in combination with adjuvant.

Modeling host responses in ferrets during A/California/07/2009 influenza infection.

Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009.