Interferon-α Production by Swine Dendritic Cells Is Inhibited During Acute Infection with Foot-and-Mouth Disease Virus

Abstract

Viruses have evolved multiple mechanisms to evade the innate immune response, particularly the actions of interferons (IFNs). We have previously reported that exposure of dendritic cells (DCs) to foot-and-mouth disease virus (FMDV) in vitro yields no infection and induces a strong type I IFN (IFN-alpha and IFN-beta) response, indicating that DCs may play a critical role in the innate response to the virus. In vivo, FMDV induces lymphopenia and reduced T-cell proliferative responses to mitogen, viral effects that may contribute to evasion of early immune responses. In this study we analyzed the in vivo effects of FMDV infection on the IFN-alpha response of two populations of dendritic cells. During the acute phase of infection of swine, production of IFN-alpha from monocyte-derived DCs (MoDCs) and skin-derived DCs (skin DCs) is inhibited. This effect occurs concurrently with rising viral titers in the blood; however, these cells are not productively infected. Interestingly, there are no changes in the capability of these DCs to take up particles and process antigens, indicating that antigen-presenting cell function is normal. These data indicate that inhibition of the IFN-alpha response of dendritic cell populations from blood and skin by FMDV enhances viral pathogenesis in infected animals.

Foot-and-Mouth Disease Virus Exhibits an Altered Tropism in the Presence of Specific Immunoglobulins, Enabling Productive Infection and Killing of Dendritic Cells

“…Our working model is that monocytes in blood are not infected either by virus alone or by FMDV IC later in infection. This agrees with the lack of replication of FMDV in PBMC (62) even in the face of high titers of live virus in blood (43). As FMDV replication occurs in the skin epithelium, monocytes will be recruited as a result of inflammation and begin to differentiate into monocyte-derived macrophages and moDC.…”

Rapid and Transient Activation of γδ T Cells to IFN-γ Production, NK Cell-Like Killing, and Antigen Processing during Acute Virus Infection

“…In FMDV infection in particular, viral clearance is most likely mediated by many aspects of innate and adaptive immune responses. Minimally, there is a significant type I IFN response mediated by various dendritic cell populations (44,45), an early Ab response (41,46,47), and the gd T cell response reported in this study. We suggest that all of these responses can work concurrently, consistent with the observation that the high viral load is cleared so early and effectively.…”

Inoculation of Swine with Foot-and-Mouth Disease SAP-Mutant Virus Induces Early Protection against Disease

“…Although FMDV can infect DC precursors in vitro, interfering with proper maturation, infection in vivo is abortive in swine (25,55) and does not affect the capability of at least skin DCs and monocyte-derived DCs (moDCs) to present antigen (25,55). Similar to infection with WT FMDV, the high levels of neutralizing antibodies and the induction of cell-mediated immunity in the animals inoculated i.d.…”