Antigen-activated dendritic cells ameliorate influenza A infections
Kobporn Boonnak, … , Eyal Talor, Kanta Subbarao
Kobporn Boonnak, … , Eyal Talor, Kanta Subbarao
Published June 24, 2013
Citation Information: J Clin Invest. 2013;123(7):2850-2861. https://doi.org/10.1172/JCI67550.
View: Text | PDF | Corrigendum
Research Article Infectious disease

Antigen-activated dendritic cells ameliorate influenza A infections

Abstract

Influenza A viruses cause significant morbidity and mortality worldwide. There is a need for alternative or adjunct therapies, as resistance to currently used antiviral drugs is emerging rapidly. We tested ligand epitope antigen presentation system (LEAPS) technology as a new immune-based treatment for influenza virus infection in a mouse model. Influenza-J-LEAPS peptides were synthesized by conjugating the binding ligand derived from the β2-microglobulin chain of the human MHC class I molecule (J-LEAPS) with 15 to 30 amino acid–long peptides derived from influenza virus NP, M, or HA proteins. DCs were stimulated with influenza-J-LEAPS peptides (influenza-J-LEAPS) and injected intravenously into infected mice. Antigen-specific LEAPS-stimulated DCs were effective in reducing influenza virus replication in the lungs and enhancing survival of infected animals. Additionally, they augmented influenza-specific T cell responses in the lungs and reduced the severity of disease by limiting excessive cytokine responses, which are known to contribute to morbidity and mortality following influenza virus infection. Our data demonstrate that influenza-J-LEAPS–pulsed DCs reduce virus replication in the lungs, enhance survival, and modulate the protective immune responses that eliminate the virus while preventing excessive cytokines that could injure the host. This approach shows promise as an adjunct to antiviral treatment of influenza virus infections.

Authors

Kobporn Boonnak, Leatrice Vogel, Marlene Orandle, Daniel Zimmerman, Eyal Talor, Kanta Subbarao

×

Figure 5

LEAPS treatment results in decreased proinflammatory cytokines and increased Th1 cytokines in the lungs of PR8-infected mice (A).

Options: View larger image (or click on image) Download as PowerPoint
LEAPS treatment results in decreased proinflammatory cytokines and incre...
On day 4 after infection, lung homogenates were analyzed for cytokine protein expression. Each data point represents the result from an individual mouse; horizontal bars indicate the mean. P values were determined by Student’s t test (***P < 0.001; **P < 0.01; *P < 0.05). Influenza-LEAPS elicit influenza-specific antibodies of the IgG2a subclass (B). Influenza-specific IgG1 and IgG2a subclass ELISA antibodies were determined in sera from PR8-infected mice collected on day 14 after infection. Infected mice were treated with DCs pulsed with NP-LEAPS, M2e-LEAPS, or combined-LEAPS influenza peptides. Control mice were infected i.n. with 100 TCID50 of PR8, and sera were collected on day 14 after infection. The error bars represent SEM for each group.