The Response of Murine Respiratory Dendritic Cells to Influenza Virus Infection

Hao, Xueli, Department of Microbiology, University of Virginia
Braciale, Thomas, Department of Microbiology, University of Virginia

Respiratory Dendritic cells (RDC) are believed to play an important role in the immune responses to the infections of respiratory tract including influenza virus. In this study, we have examined the susceptibility of isolated murine RDC to influenza virus infection, the effect of multiplicity of infection on their costimulatory ligand upregulation and inflammatory cytokine and chemokine production, and their capacity to stimulate T cell responses. We find that the efficiency of RDC infection is dependent on the multiplicity of infection (MOI) and not all RDC are equally susceptible to infection. Upregulation of the expression of several costimulatory ligands is suppressed in highly susceptible RDC. Further studies show that susceptibility to infection is correlated with different RDC subsets with CD103 + DC being the most susceptible, CD103 - CD11b hi DC intermediate and plasmacytoid DC (PDC) least susceptible to infection. These three RDC subsets show differential cytokine production to influenza virus infection: PDC are the major producers of a variety of cytokines/chemokines i.e., IFN-, IL-12p40, IL-6, KC, and MIP- . CD103 + DC are the predominant producers of KC and IL-12p40, while CD103 - CD11b hi DC are the dominant producers of RANTES. Furthermore, we demonstrate that CD103 + DC are more efficient at stimulating CD8 + T cell proliferation than CD103 - CD11b hi DC at low dose influenza virus infection. In addition, we show that CD103 + DC are intrinsically more efficient at stimulating CD8 + T cell proliferation than CD103 - CD11b hi DC. However, we do not observe any differences in the expression of activation markers, adhesion markers, and effector cytokines by activated CD8 + T cells stimulated by the two RDC subsets. Consistent with a previous report, our preliminary data iii also suggest peptide-pulsed CD103 - CD11b hi DC are more efficient at stimulating CD4 + T cell proliferation than CD103 + DC at low dose. In conclusion, our results indicate that distinct RDC subsets differ in their susceptibility to infection, in the expression of infection induced inflammatory mediators, and in their ability to stimulate CD8 + T responses. Our data suggest that a complete immune response and, therefore full clinical recovery from influenza virus infection, likely depends on the coordinated response of three distinct RDC subsets, each playing a unique role.

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PHD (Doctor of Philosophy)
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