Infection of porcine bone marrow-derived macrophages by porcine respiratory and reproductive syndrome virus impairs phagosomal maturation

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV), a positive-sense, ssRNA virus of the genus Arterivirus, is a devastating disease of swine worldwide. Key early targets of PRRSV infection in pigs include professional phagocytes in the lung, such as alveolar and interstitial macrophages and dendritic cells, the dysfunction of which is believed to be responsible for much of the associated mortality. In order to study the effect of virus infection on phagocyte function, the development of a robust, reproducible model would be advantageous. Given the limitations of current models, we set out to develop a porcine bone marrow-derived macrophage (PBMMW) cell model to study phagosomal maturation and function during PRRSV infection. Derivation of PBMMWs from marrow using cultured L929 fibroblast supernatant produced a homogeneous population of cells that exhibited macrophage-like morphology and proficiency in Fc-receptor-mediated phagocytosis and phagosomal maturation. PBMMWs were permissive to PRRSV infection, resulting in a productive infection that peaked at 24 h. Assessment of the effect of PRRSV infection on the properties of phagosomal maturation in PBMMWs revealed a significant decrease in phagosomal proteolysis and lowered production of reactive oxygen species, but no change in PBMMW viability, phagocytosis or the ability of phagosomes to acidify. In this study, we present a new model to investigate PRRSV infection of phagocytes, which demonstrates a significant effect on phagosomal maturation with the associated implications on proper macrophage function. This model can also be used to study the effect on the phagosomal microenvironment of infection by other viruses targeting porcine macrophages.

β2-adrenoreceptor stimulation dampens the LPS-induced M1 polarization in pig macrophages

“…In agreement with previous data, we found that BMM displayed anti-microbial functions such as phagocytosis of bacteria, phagosome acidification and ROS production (Chaudhuri et al, 2016). In rodents, catecholamines were previously shown to increase the phagocytic capacity of macrophages (Baccan et al, 2010;Xiu et al, 2013;Grailer et al, 2014), which was suggested to rely upon b2-AR stimulation (Muthu et al, 2010).…”

Transcriptome Analysis Reveals Dynamic Gene Expression Profiles in Porcine Alveolar Macrophages in Response to the Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

“…PRRSV infection is shown to impair the phagosomal maturation of PAMs [90]. Similar to the previous study [18], our analyses also identified that a great variety of phagocytosis-promoting receptor genes were significantly decreased, implying that PRRSV infection can impair the receptor-mediated uptake process of phagocytosis of PAMs.…”

Improved Vaccine against PRRSV: Current Progress and Future Perspective

“…Unlike other members of Arterivirus , which have relatively broad tropisms for cells of various origins ( Zhang and Yoo, 2015 ), PRRSV infection is highly restricted to cells of the monocyte-macrophage lineage, such as porcine alveolar macrophages (PAMs) ( Albina et al, 1998 ; Morgan et al, 2014 ), macrophages from the spleen, tonsils, lymph nodes, liver, Peyer’s patches and thymus, as well as peritoneal macrophages from blood and progenitor cells in bone marrow ( Sur et al, 1996 ; Duan et al, 1997a , b ; Wang et al, 2016 ). Moreover, bone marrow-derived dendritic cells and macrophages are susceptible to PRRSV infection in vitro as well ( Chang et al, 2008 ; Chaudhuri et al, 2016 ). Generally, only PAMs in lung are considered to be the primary target of PRRSV in vivo ( Albina et al, 1998 ; Morgan et al, 2014 ).…”