title: Differential type I interferon activation and susceptibility of dendritic cell populations to porcine arterivirus.
abstract: Dendritic cells (DCs) play a role in anti-viral immunity by providing early innate protection against viral replication and by presenting antigen to T cells for initiation of the adaptive immune response. Studies show the adaptive response to porcine reproductive and respiratory syndrome virus (PRRSV) is ineffective for complete viral elimination. Other studies describe the kinetics of the adaptive response to PRRSV, but have not investigated the early response by DCs. We hypothesize that there is an aberrant activation of DCs early in PRRSV infection; consequently, the adaptive response is triggered inadequately. The current study characterized a subtype of porcine lung DCs (L-DCs) and investigated the ability of PRRSV to infect and replicate in L-DCs and monocyte-derived DCs (MDDCs). Furthermore, the type I interferon anti-viral response to PRRSV with and without the addition of recombinant porcine IFN-alpha (rpIFN-alpha), an important cytokine that signals for anti-viral mediator activation, was analysed. Results show that PRRSV replicated in MDDCs but not L-DCs, providing evidence that these cells have followed distinct differentiation pathways. Although both cell types responded to PRRSV with an induction of IFN-beta mRNA, the magnitude and duration of the response differed between cell types. The addition of rpIFN-alpha was protective in MDDCs, and mRNA synthesis of Mx (myxovirus resistant) and PKR (double-stranded RNA dependent protein kinase) was observed in both cell types after rpIFN-alpha addition. Overall, PRRSV replicated in MDDCs but not L-DCs, and rpIFN-alpha was required for the transcription of protective anti-viral mediators. DC response to PRRSV was limited to IFN-beta transcription, which may be inadequate in triggering the adaptive immune response.
authors.affiliation: Immunobiology Graduate Program, Iowa State University, Ames, Iowa, USA.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Loving
authors.forename: Susan L
authors.initials: SL
authors.lastname: Brockmeier
authors.forename: Randy E
authors.initials: RE
authors.lastname: Sacco
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000648:ultrastructure / Q000821:virology*; D004198:Disease Susceptibility; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000166:cytology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000472:pathogenicity* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D034421:Sus scrofa; D014774:Virulence; D014779:Virus Replication / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta