Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity

Abstract

The New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathogenic Lassa virus replicates but fails to activate human macrophages. Less is known in regard to the impact of New World arenavirus infection on the human macrophage immune response. Macrophage activation is critical for controlling infections but could also be usurped favoring immune evasion. Therefore, it is crucial to understand how the JUNV infection modulates macrophage plasticity to clarify its role in AHF pathogenesis. With this aim in mind, we compared infection with the attenuated Candid 1 (C#1) or the pathogenic P strains of the JUNV virus in human macrophage cultures. The results showed that both JUNV strains similarly replicated and induced morphological changes as early as 1 day post-infection. However, both strains differentially induced the expression of CD71, the receptor for cell entry, the activation and maturation molecules CD80, CD86, and HLA-DR and selectively modulated cytokine production. Higher levels of TNF-α, IL-10, and IL-12 were detected with C#1 strain, while the P strain induced only higher levels of IL-6. We also found that C#1 strain infection skewed macrophage polarization to M1, whereas the P strain shifted the response to an M2 phenotype. Interestingly, the MERTK receptor, that negatively regulates the immune response, was down-regulated by C#1 strain and up-regulated by P strain infection. Similarly, the target genes of MERTK activation, the cytokine suppressors SOCS1 and SOCS3, were also increased after P strain infection, in addition to IRF-1, that regulates type I IFN levels, which were higher with C#1 compared with P strain infection. Together, this differential activation/polarization pattern of macrophages elicited by P strain suggests a more evasive immune response and may have important implications in the pathogenesis of AHF and underpinning the development of new potential therapeutic strategies.

Transcriptomic Analysis of Chicken Lungs Infected With Avian and Bovine Pasteurella multocida Serotype A

“…However, the different outcomes of chicken challenged with PmCQ2 and PmQ hint that macrophage may play different roles. For example, NOS2, a key marker, and PTX3 and IRF5, two important regulators of M1 macrophage activation (51)(52)(53), were significantly overexpressed in PmQ infected chicken, tending to activate to more pro-inflammatory activation. Whereas, in the PmCQ2 infected chicken lung, M2 markers (MRC1LD, MRC1LB, and MACRO) and M1 markers (CD86 and CD80) were upregulated, implying a mixed activation of both M1 and M2 macrophage occurred.…”

MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism

“…Although the role of miRNA in mammarenavirus pathogenesis is not clear, its role in regulating important molecular pathways during infection cannot be ruled out as an important mechanism to be further investigated. In addition, many studies have suggested that a multifactor pathway could be involved in the different outcomes from arenaviral infection including a relatively low number of adaptive mutations, as well as the incapacity to bind to human receptors and different immune responses elicited by these viruses [ 91 , 92 , 93 ].…”

A Heterotypic Tridimensional Model to Study the Interaction of Macrophages and Glioblastoma In Vitro

“…Peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteer donors who had given written consent and has not taken any non-steroidal anti-inflammatory drugs for 10 days prior to sampling, as previously described [ 5 , 8 , 32 ]. Briefly, PBMCs from healthy donors were isolated by Ficoll-Hypaque (GE, Chicago, IL, USA) density gradient centrifugation, and a positive selection of CD14+ monocytes was performed using an EasySep Human CD14 Positive Selection Kit (StemCell Tech, Vancouver, BC, Canada) as indicated by the manufacturer.…”