Plasmacytoid dendritic cell activation by foot‐and‐mouth disease virus requires immune complexes

Abstract

Natural IFN-producing cells (NIPC), also called plasmacytoid dendritic cells, represent an essential component of the innate immune defense against infection. Despite this, not much is known about the pathways involved in their activation by non-enveloped viruses. The present study demonstrates that the non-enveloped foot-and-mouth disease virus (FMDV) cannot stimulate IFN-alpha responses in NIPC, unless complexed with FMDV-specific immunoglobulins. Stimulation of NIPC with such immune complexes employs FcgammaRII ligation, leading to strong secretion of IFN-alpha. In contrast to the stimulation of NIPC by many enveloped viruses, FMDV induction of IFN-alpha production requires live virus. It is necessary for the virus to initiate its replicative cycle. Moreover, it is an abortive replication, as witnessed by the decrease of dsRNA levels and viral titers with time post infection. Sensitivity of the NIPC stimulation to wortmannin and chloroquin, but not leupeptin, indicates an essential role for the pre-lysosomal stage endosomal compartment. In conclusion, the present study demonstrates that immune complexes provide the means for a non-interferogenic virus to induce IFN-alpha responses by NIPC. This indicates an important link between NIPC and antibodies in immune responses against non-enveloped viruses such as FMDV.

Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA

“…HAV must have an additional advantage over HCV, however, to account for the dramatic difference that we have demonstrated in the IFN response to acute infection. Unlike enveloped viruses, the activation of pDCs by picornaviruses appears to require the presence of anti-viral antibodies (38,39). Although the pDC response to HAV has not been studied, the weak induction of ISGs by HAV could reflect a failure of pDCs to sense infection.…”

Human pDCs preferentially sense enveloped hepatitis A virions

“…Nonetheless, some picornaviruses (aphthoviruses and some strains of coxsackievirus B) activate pDCs only in the presence of antiviral antibodies, suggesting that uptake of the virus is limiting and requires Fc receptors (9,10). Internalization thus appears to be critical for sensing of picornaviruses by pDCs, while replication of the viral genome is not always required.…”

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

“…Similarly, infection of porcine macrophages-monocytes occurred in the presence of antibodycomplexed FMDV, but not with virus alone (6). Such interactions may have important functional consequences for immunity, for example, porcine natural-interferon (IFN)-producing cells require immune-complexed FMDV to induce type I IFN production in vitro (22).…”