Sensing of Porcine Reproductive and Respiratory Syndrome Virus-Infected Macrophages by Plasmacytoid Dendritic Cells.

Garcia Nicolas, Obdulio; Auray, Gael; Sautter, Carmen Alexandra Nadine; Rappe, Julie Christiane Françoise; McCullough, Kenneth; Ruggli, Nicolas; Summerfield, Artur (2016). Sensing of Porcine Reproductive and Respiratory Syndrome Virus-Infected Macrophages by Plasmacytoid Dendritic Cells. Frontiers in Microbiology, 7(771), p. 771. Frontiers 10.3389/fmicb.2016.00771

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Porcine reproductive and respiratory syndrome virus (PRRSV) represents a macrophage (MØ)-tropic virus which is unable to induce interferon (IFN) type I in its target cells. Nevertheless, infected pigs show a short but prominent systemic IFN alpha (IFN-α) response. A possible explanation for this discrepancy is the ability of plasmacytoid dendritic cells (pDC) to produce IFN-α in response to free PRRSV virions, independent of infection. Here, we show that the highly pathogenic PRRSV genotype 1 strain Lena is unique in not inducing IFN-α production in pDC, contrasting with systemic IFN-α responses found in infected pigs. We also demonstrate efficient pDC stimulation by PRRSV Lena-infected MØ, resulting in a higher IFN-α production than direct stimulation of pDC by PRRSV virions. This response was strain-independent, required integrin-mediated intercellular contact, intact actin filaments in the MØ and was partially inhibited by an inhibitor of neutral sphingomyelinase. Although infected MØ-derived exosomes stimulated pDC, an efficient delivery of the stimulatory component was dependent on a tight contact between pDC and the infected cells. In conclusion, with this mechanism the immune system can efficiently sense PRRSV, resulting in production of considerable quantities of IFN-α. This is adding complexity to the immunopathogenesis of PRRSV infections, as IFN-α should alert the immune system and initiate the induction of adaptive immune responses, a process known to be inefficient during infection of pigs.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Garcia Nicolas, Obdulio; Auray, Gael; Sautter, Carmen Alexandra Nadine; Rappe, Julie Christiane Françoise; McCullough, Kenneth; Ruggli, Nicolas and Summerfield, Artur

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology

ISSN:

1664-302X

Publisher:

Frontiers

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

23 Mar 2017 14:07

Last Modified:

02 Apr 2017 02:21

Publisher DOI:

10.3389/fmicb.2016.00771

PubMed ID:

27458429

Uncontrolled Keywords:

IFN-α; PRRSV; intercellular communication; macrophages; plasmacytoid dendritic cells

BORIS DOI:

10.7892/boris.96418

URI:

https://boris.unibe.ch/id/eprint/96418

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