Autocrine Type I IFN and Contact with Endothelium Promote the Presentation of Influenza A Virus by Monocyte-Derived APC

Abstract

Purified monocytes infected with influenza A virus do not become mature dendritic cells (DCs) and they present viral peptides poorly to autologous memory T cells. In this study, we investigated whether influenza A-infected monocytes matured to DCs with a high capacity to stimulate T cells when they were infected with influenza A virus in a model tissue setting wherein they were cocultured with endothelium grown on a type I collagen matrix. Intercellular interactions with endothelium strongly promoted the Ag-presenting capacity of monocyte-derived cells infected with influenza A virus, and the heterologous coculture system also enhanced production of IFN-α by monocytes in the absence of plasmacytoid cells. Production of IFN-α in the presence of endothelium correlated with monocyte differentiation to mature DCs and their ability to stimulate proliferation and IFN-γ production by autologous T cells. Monocyte-derived cells that developed into migratory DCs promoted proliferation of influenza A virus-specific CD4+ and CD8+ cells, whereas those that developed into macrophages promoted proliferation of CD8+ T cells only. This onset of APC activity could be partially blocked with Ab to the IFN-αβ receptor when monocytes were infected with UV-treated virus, but neutralizing this pathway was inconsequential when monocytes were infected with live virus. Thus, type I IFN and direct contact with endothelium promote development of influenza A virus-presenting activity in monocyte-derived cells in a setting in which this differentiation does not depend on plasmacytoid cells. However, when infected with live influenza virus, the role of type I IFN in mediating differentiation and Ag-presenting capacity is expendable, apparently due to other mechanisms of virus-mediated activation.

Mycobacterium tuberculosisDiverts Alpha Interferon-Induced Monocyte Differentiation from Dendritic Cells into Immunoprivileged Macrophage-Like Host Cells

“…Thus, the inflammatory milieu induced by M. tuberculosis might be enriched with IFN-␣ that, in turn, could favor the differentiation of recruited monocytes into DCs (40). The autocrine secretion of IFN-␣ has also been suggested to be a modulator of monocyte differentiation in a model tissue setting in which monocytes were cocultured with endothelium grown on a type I collagen matrix (35). In this regard, in vivo experiments clearly indicated that M. tuberculosis strains with the ability to induce IFN-␣ displayed increased virulence and a capacity to induce disease (26,27).…”

Relationships Among Murine CD11chigh Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns

“…However, we have found that this is stimulus dependent and that, when appropriately stimulated, nonplasmacytoid mouse DC also produce high amounts of IFN␣. 5 Similarly, nonplasmacytoid human monocyte-derived DC produce type I IFN in response to infection with influenza (43,44).…”

Overlap between Systemic Lupus Erythematosus and Kikuchi Fujimoto Disease

“…In patients with lupus, there is an association between disease activity and type I IFN levels in the peripheral blood [24][25][26][27]. Not all lupus patients have measurably increased levels of type 1 IFN, but they may have increased type 1 IFN-responsive gene expression "signatures" in blood mononuclear cells [16,18]. This suggests that these cells have been exposed to high levels of type 1 IFN elsewhere (e.g., in the tissues).…”

“…In both disorders the lymph node pathology can show histiocytic necrotizing lymphadenitis, and in both, the plasmacytoid histiocyte or PDC plays a role. In the lymph node, PDCs are localized to the "T zone," which is centered around the high endothelial venules [15], where they also present antigen [16]. The pathology in KFD often centers around T zone of the lymph node [17], although in this case, the lymph node architecture was not preserved and the T zone was not clearly seen.…”