Dynamic changes in bronchoalveolar macrophages and cytokines during infection of pigs with a highly or low pathogenic genotype 1 PRRSV strain

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) replicates primarily in pulmonary alveolar macrophages (PAMs) and the resulting lung damage is influenced by strain virulence. To better understand the pathogenesis of PRRSV infection, we performed a longitudinal study of the PAM population and lung cytokines in specific pathogen-free pigs infected either with the highly pathogenic Lena strain or with the low pathogenic Finistere strain in comparison to uninfected pigs. Bronchoalveolar lavage fluid (BALF) and blood were collected to follow viral, cellular and cytokine changes in lung with respect to clinical signs and systemic events. Compared to Finistere-infected pigs, Lena-infected pigs exhibited more severe clinical signs and 10- to 100-fold higher viral loads in BALF and blood. Similarly, they showed an earlier drop in BALF cell viability and phagocytic activity along with a decrease in the macrophage count. From 8 to 15 days post-infection (dpi), monocytes increased both in BALF and blood from Lena-infected pigs. BALF and blood showed contrasting cytokine patterns, with low increase of IFN-α and TNF-α levels and high increase for IL-1α and IL-8 in BALF after Lena-infection. In contrast, in the blood, the increase was marked for IFN-α and TNF-α but limited for IL-1β and IL-8. Down-regulation of PAM functions combined with inflammatory cytokine and monocyte recruitment may promote lung pathogenesis and virus replication in PRRSV infections with the highly pathogenic Lena strain. In contrast, the low pathogenic Finistere strain showed prolonged viral replication in lung, possibly related to the weak IFN-γ response.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-017-0420-y) contains supplementary material, which is available to authorized users.

Porcine Alveolar Macrophage-like cells are pro-inflammatory Pulmonary Intravascular Macrophages that produce large titers of Porcine Reproductive and Respiratory Syndrome Virus

“…At day 10 post PRRSV infection, we observed a significant increase in the percentage of dead cells of these two populations (Fig. 4a ) as previously described for AM 28 . Moreover, in agreement with this result, the proportion of AM and PIM/AM-like cells among MHC-II high BAL and parenchymal cells respectively decrease (Fig.…”

“…Our in vitro data prompted us to measure the infection of PIM/AM-like cells during in vivo PRRSV infection. We chose to measure AM and PIM/AM-like cells PRRSV infection at an intermediate time point of 10 days post-infection (dpi), at which LENA viremia had reach a plateau 28 . We first measured the percentage of dead cells in PIM/AM-like cells and AM populations.…”

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

“…PI staining of the CD163 + BAL cells revealed that the decrease in the CD163 + cell population was due to cell death. A similar reduction in the macrophage population after PRRSV-1 infection was previously reported [48]. Following the strategy described previously [11], different subsets of DC and macrophages were identified in BAL cells, and the changes in the populations of these subsets during disease progression were studied.…”

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

“…PRRSV-1.3 such as Lena, are more pathogenic than PRRSV-1.1 as Lelystad virus (LV) ( 3 – 6 ). The infection by PRRSV-1.3 is characterized by higher body temperature, more sever clinical signs and lung pathology compared to PRRSV-1.1, whereas viremia and lung viral load are not consistently higher ( 5 , 7 ).…”