Porcine Reproductive and Respiratory Syndrome Virus Type 1.3 Lena Triggers Conventional Dendritic Cells 1 Activation and T Helper 1 Immune Response Without Infecting Dendritic Cells

Abstract

Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is an arterivirus responsible for highly contagious infection and huge economic losses in pig industry. Two species, PRRSV-1 and PRRSV-2 are distinguished, PRRSV-1 being more prevalent in Europe. PRRSV-1 can further be divided in subtypes. PRRSV-1.3 such as Lena are more pathogenic than PRRSV-1.1 such as Lelystad or Flanders13. PRRSV-1.3 viruses trigger a higher Th1 response than PRRSV-1.1, although the role of the cellular immune response in PRRSV clearance remains ill defined. The pathogenicity as well as the T cell response inductions may be differentially impacted according to the capacity of the virus strain to infect and/or activate DCs. However, the interactions of PRRSV with in vivo-differentiated-DC subtypes such as conventional DC1 (cDC1), cDC2, and monocyte-derived DCs (moDC) have not been thoroughly investigated. Here, DC subpopulations from Lena in vivo infected pigs were analyzed for viral genome detection. This experiment demonstrates that cDC1, cDC2, and moDC are not infected in vivo by Lena. Analysis of DC cytokines production revealed that cDC1 are clearly activated in vivo by Lena. In vitro comparison of 3 Europeans strains revealed no infection of the cDC1 and cDC2 and no or little infection of moDC with Lena, whereas the two PRRSV-1.1 strains infect none of the 3 DC subtypes. In vitro investigation of T helper polarization and cytokines production demonstrate that Lena induces a higher Th1 polarization and IFNγ secretion than FL13 and LV. Altogether, this work suggests an activation of cDC1 by Lena associated with a Th1 immune response polarization.

Evaluation of local and systemic immune responses in pigs experimentally challenged with porcine reproductive and respiratory syndrome virus

“…Moreover, CD172a + /CD163 − /MHC-II + and CD172a − /CD163 − / MHC-II + cells exhibit strong migration and antigenpresenting capabilities [10], which can be credited to the increased influx of these cells into the lungs during the course of infection. Our results were in agreement with those obtained in previous studies, which found that the populations of these cells are increased in the BAL after PRRSV-1 infection [8]. Interestingly, cDC1s activate allogenic naïve T cells and aid induction of the Th1 response, whereas cDC2s induce a Th2 response in pigs [10].…”

“…Therefore, dissecting how these immune cells respond to PRRSV infection is important to better understand the nature of PRRS. Until now, limited studies have investigated the alterations in the respiratory DC/macrophage network in pigs during disease progression [8,10], and the association of the alteration in this immune network with the T-cell response has not been reported. Here, we attempted to explore the dynamics of this important host defence mechanism in relation to PRRSV infection.…”

“…The interactions between PRRSV and host immune responses have been widely studied, but most studies investigated systemic immune responses using PBMC and/or serum [7]. Previous studies have shown that interstitial pneumonia constitutes the major lung lesions in PRRSV-infected pigs and that significantly decreased numbers of alveolar macrophages are found in bronchoalveolar lavage (BAL) and lung parenchyma samples from PRRSV-infected pigs [8]. However, to the best of our knowledge, the kinetics of local immune responses in the lungs or lymph nodes during the course of infection compared with those of peripheral immune responses have not been previously studied.…”

“…This network is predominantly involved in sensing foreign antigens, controlling inflammation, and initiating the adaptive immune response [10]. Different DC subsets with specific functional specializations exist in the respiratory DC/macrophage network in the lungs and are reportedly resistant to PRRSV infection [8,11]. However, upon activation, these DC travel to lymphoid tissues to present antigen to T lymphocytes and thereby serve as the link between innate and adaptive immunity [10,11].…”

Development of Pig Conventional Dendritic Cells From Bone Marrow Hematopoietic Cells in vitro

“…ITGAX (CD11c) was highly expressed on macrophages as well, but lower on the putative cDC1, cDC2, and CD14 + DCs. This is contrary to the result of pig blood cDCs ( 22 ) but somewhat consistent with the analysis of lung DCs ( 28 ).…”