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Simple Summary: This study investigates the autoimmune effects of gold aurothiomalate (AuTM) exposure in genetically different mouse strains to understand how gold triggers autoimmune diseases. We focused on two strains, A.TL and A.SW, which share genetic similarities except for H-2-related genes. Here, we show that A.TL mice, when exposed to AuTM, developed specific immune responses, including increased levels of antinuclear antibodies (ANA) compared to A.SW mice. A.TL mice showed a particularly strong response, especially in females, resembling symptoms of human autoimmune diseases like lupus. These findings suggest that A.TL mice could be a valuable model for studying environment-induced autoimmunity, helping to explore the genetic mechanisms behind these conditions and potentially leading to improved diagnosis and treatment of autoimmune diseases in humans. To demonstrate causation or/and assess pathogenic mechanisms of environment-induced autoimmunity, various animal models that mimic the characteristics of the human autoimmune diseases need to be developed. Experimental studies in mice reveal the genetic factors that contribute to autoimmune diseases. Here, the immune response of two mouse strains congenic for non-H-2 genes, A.TL (H-2tl) and A.SW (H-2s), was evaluated after 15 weeks' exposure to gold aurothiomalate (AuTM). AuTM-treated A.TL mice showed anti-nuclear antibodies (ANA) with homogenous and/or fine speckled staining patterns and serum autoantibodies to ds-DNA, chromatin, histones, and ribonucleoproteins (RNP). Female A.TL mice showed a stronger immune response than males, as well as an increase of B cells in their spleen after 15 weeks of gold exposure. A.SW exposed for AuTM showed the induction of anti-nucleolar antibodies (ANoA) with a clumpy staining pattern, as well as an increase in splenic B and T cells. The serum autoantibodies levels in A.SW mice were limited compared to those of A.TL mice. Overall, A.TL presents a stronger immune response after gold exposure than A.SW. The immune response developed in A.TL presents similarities with the clinical manifestations in human autoimmune diseases. Thus, gold-exposed A.TL could constitute a potential experimental mouse model for the study of autoimmunity. [ABSTRACT FROM AUTHOR]

Fish Red-Blood Cells (RBCs) are nucleated cells that can modulate the expression of different sets of genes in response to stimuli, playing an active role in the homeostasis of the fish immune system. Nowadays, vaccination is one of the main ways to control and prevent viral diseases in aquaculture and the development of novel vaccination approaches is a focal point in fish vaccinology. One of the strategies that has recently emerged is the use of nanostructured recombinant proteins. Nanostructured cytokines have already been shown to immunostimulate and protect fish against bacterial infections. To explore the role of RBCs in the immune response to two nanostructured recombinant proteins, TNF α and a G-VHSV protein fragment, we performed different in vitro and in vivo studies. We show for the first time that rainbow trout RBCs are able to endocytose nanostructured TNF α and G-VHSV protein fragment in vitro , despite not being phagocytic cells, and in response to nanostructured TNF α and G-VHSV fragment, the expression of different immune genes could be modulated. [ABSTRACT FROM AUTHOR]

In recent years, fish nucleated red blood cells (RBCs) have been implicated in the response against viral infections. We have demonstrated that rainbow trout RBCs can express the antigen encoded by a DNA vaccine against viral hemorrhagic septicemia virus (VHSV) and mount an immune response to the antigen in vitro. In this manuscript, we show, for the first time, the role of RBCs in the immune response triggered by DNA immunization of rainbow trout with glycoprotein G of VHSV (GVHSV). Transcriptomic and proteomic profiles of RBCs revealed genes and proteins involved in antigen processing and presentation of exogenous peptide antigen via MHC class I, the Fc receptor signaling pathway, the autophagy pathway, and the activation of the innate immune response, among others. On the other hand, GVHSV-transfected RBCs induce specific antibodies against VHSV in the serum of rainbow trout which shows that RBCs expressing a DNA vaccine are able to elicit a humoral response. These results open a new direction in the research of vaccination strategies for fish since rainbow trout RBCs actively participate in the innate and adaptive immune response in DNA vaccination. Based on our findings, we suggest the use of RBCs as target cells or carriers for the future design of novel vaccine strategies. [ABSTRACT FROM AUTHOR]

Teleost red blood cells (RBCs) are nucleated and therefore can propagate cellular responses to exogenous stimuli. RBCs can mount an immune response against a variety of fish viruses, including the viral septicemia hemorrhagic virus (VHSV), which is one of the most prevalent fish viruses resulting in aquaculture losses. In this work, RBCs from blood and head kidney samples of rainbow trout challenged with VHSV were analyzed via transcriptomic and proteomic analyses. We detected an overrepresentation of differentially expressed genes (DEGs) related to the type I interferon response and signaling in RBCs from the head kidney and related to complement activation in RBCs from blood. Antigen processing and presentation of peptide antigen was overrepresented in RBCs from both tissues. DEGs shared by both tissues showed an opposite expression profile. In summary, this work has demonstrated that teleost RBCs can modulate the immune response during an in vivo viral infection, thus implicating RBCs as cell targets for the development of novel immunomodulants. [ABSTRACT FROM AUTHOR]

Background: It has been described that fish nucleated red blood cells (RBCs) generate a wide variety of immune-related gene transcripts when viruses highly replicate inside them and are their main target cell. The immune response and mechanisms of fish RBCs against viruses targeting other cells or tissues has not yet been explored and is the objective of our study. Methods: Rainbow trout RBCs were obtained from peripheral blood, ficoll purified and exposed to Viral Haemorrhagic Septicaemia virus (VHSV). Immune response was evaluated by means of RT-qPCR, flow cytometry, immunofluorescence and isobaric tag for relative and absolute quantification (iTRAQ) protein profiling. Results: VHSV N gene transcripts incremented early postexposure and were drastically decreased after 6 hours postexposure (hpe). The expression of type I interferon ( ifn1 ) gene was significantly downregulated at early postexposure (3 hpe), together with a gradual downregulation of interferon-inducible mx and pkr genes until 72 hpe. Type I IFN protein was downregulated and interferon-inducible Mx protein was maintained at basal levels. Co-culture assays of RBCs, previously exposed to UV-inactivated VHSV, and TSS (stromal cell line from spleen) revealed IFN crosstalk between both cell types. On the other hand, anti-microbial peptide β-defensin 1 and neutrophil chemotactic factor interleukin 8 were slightly upregulated in VHSV-exposed RBCs. iTRAQ profiling revealed that VHSV exposure can induce a global protein downregulation in rainbow trout RBCs, mainly related to RNA stability and proteasome pathways. Antioxidant/antiviral response is also suggested to be involved in the response of rainbow trout RBCs to VHSV. Conclusions: A variety of mechanisms are proposed to be implicated in the antiviral response of rainbow trout RBCs against VHSV halted infection. Ongoing research is focused on understanding the mechanisms in detail., Competing Interests: No competing interests were disclosed.