scholarly journals Identification of diverse defense mechanisms in trout red blood cells in response to VHSV halted viral replication

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1958 ◽  
Author(s):  
Ivan Nombela ◽  
Sara Puente-Marin ◽  
Veronica Chico ◽  
Alberto J. Villena ◽  
Begoña Carracedo ◽  
...  
Keyword(s):  
Immune Response ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Absolute Quantification ◽  
Antiviral Response ◽  
Protein Profiling ◽  
Type I ◽  
Ongoing Research ◽  
Isobaric Tag ◽  
Gene Transcripts

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:Trout RBCs were obtained from peripheral blood, ficoll purified and exposed toViral 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 profilingResults:VHSV N gene transcripts incremented early postexposure and were drastically decreased after 6 hours postexposure (hpe). The expression of the type I interferon (ifn1) gene was significantly downregulated at early postexposure (3 hpe), together with a gradual downregulation of interferon-induciblemxandpkrgenes until 72 hpe. Type I IFN protein was downregulated and interferon-inducible Mx protein was maintained at basal levels. Co-culture assays of RBCs with TSS (stromal cell line from spleen) revealed the 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 Isobaric tag for relative and absolute quantification (iTRAQ) revealed that VHSV exposure can induce a global protein downregulation in trout RBCs, mainly related to RNA stability and proteasome pathways. The antioxidant/antiviral response is also suggested to be involved in the response of trout RBCs to VHSV.Conclusions:A variety of mechanisms are proposed to be implicated in the antiviral response of trout RBCs against VHSV halted infection. Ongoing research is focused on understanding the mechanisms in detail. To our knowledge, this is the first report that implicates fish RBCs in the antiviral response against viruses not targeting RBCs.

scholarly journals Identification of diverse defense mechanisms in rainbow trout red blood cells in response to halted replication of VHS virus

F1000Research ◽  
2018 ◽  
Vol 6 ◽  
pp. 1958 ◽  
Author(s):  
Ivan Nombela ◽  
Sara Puente-Marin ◽  
Veronica Chico ◽  
Alberto J. Villena ◽  
Begoña Carracedo ◽  
...  
Keyword(s):  
Immune Response ◽  
Rainbow Trout ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Antiviral Response ◽  
Protein Profiling ◽  
N Gene ◽  
Type I ◽  
Ongoing Research ◽  
Gene Transcripts

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 toViral 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-induciblemxandpkrgenes 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.

scholarly journals Integrated Transcriptomic and Proteomic Analysis of Red Blood Cells from Rainbow Trout Challenged with VHSV Point Towards Novel Immunomodulant Targets

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 63 ◽  
Author(s):  
Nombela ◽  
Lopez-Lorigados ◽  
Salvador-Mira ◽  
Puente-Marin ◽  
Chico ◽  
...  
Keyword(s):  
Immune Response ◽  
Rainbow Trout ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Antigen Processing ◽  
Head Kidney ◽  
Interferon Response ◽  
Type I ◽  
Fish Viruses

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.

scholarly journals Infectious pancreatic necrosis virus triggers antiviral immune response in rainbow trout red blood cells, despite not being infective

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1968 ◽  
Author(s):  
Ivan Nombela ◽  
Aurora Carrion ◽  
Sara Puente-Marin ◽  
Veronica Chico ◽  
Luis Mercado ◽  
...  
Keyword(s):  
Immune Response ◽  
Rainbow Trout ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Pancreatic Necrosis ◽  
Antiviral Response ◽  
Infectious Pancreatic Necrosis Virus ◽  
Necrosis Virus ◽  
Infectious Pancreatic Necrosis ◽  
Pancreatic Necrosis Virus

Background: Some fish viruses, such as piscine orthoreovirus and infectious salmon anemia virus, target red blood cells (RBCs), replicate inside them and induce an immune response. However, the roles of RBCs in the context of infectious pancreatic necrosis virus (IPNV) infection  have not been studied yet.Methods: Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll purified and exposed to IPNV in order to analyze infectivity and immune response using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting techniques.Results: IPNV could not infect RBCs; however, IPNV increased the expression of the INF1-related genesifn-1,pkrandmxgenes. Moreover, conditioned media from IPNV-exposed RBCs conferred protection against IPNV infection in CHSE-214 fish cell line.Conclusions: Despite not being infected, rainbow trout RBCs could respond to IPNV with increased expression of antiviral genes. Fish RBCs could be considered as mediators of the antiviral response and therefore targets of new strategies against fish viral infections. Further research is ongoing to completely understand the molecular mechanism that triggers this antiviral response in rainbow trout RBCs.

scholarly journals CELLS INVOLVED IN THE IMMUNE RESPONSE

1969 ◽  
Vol 129 (4) ◽  
pp. 757-774 ◽  
Author(s):  
Nabih I. Abdou ◽  
Maxwell Richter
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
Allogeneic Bone Marrow ◽  
Red Cells ◽  
Allogeneic Bone ◽  
Sheep Red Blood Cells ◽  
Sheep Red Cells

Irradiated rabbits given allogeneic bone marrow cells from normal adult donors responded to an injection of sheep red blood cells by forming circulating antibodies. Their spleen cells were also capable of forming many plaques using the hemolysis in gel technique, and were also capable of undergoing blastogenesis and mitosis and of incorporating tritiated thymidine upon exposure to the specific antigen in vitro. However, irradiated rabbits injected with allogeneic bone marrow obtained from rabbits injected with sheep red blood cells 24 hr prior to sacrifice (primed donors) were incapable of mounting an immune response after stimulation with sheep red cells. This loss of reactivity by the bone marrow from primed donors is specific for the antigen injected, since the immune response of the irradiated recipients to a non-cross-reacting antigen, the horse red blood cell, is unimpaired. Treatment of the bone marrow donors with high-titered specific antiserum to sheep red cells for 24 hr prior to sacrifice did not result in any diminished ability of their bone marrow cells to transfer antibody-forming capacity to sheep red blood cells. The significance of these results, with respect to the origin of the antigen-reactive and antibody-forming cells in the rabbit, is discussed.

scholarly journals Evaluation of cellular immune response in Golden Hamsters experimentally infected with Leishmania donovani comparing with cellular immune response against chicken Red Blood Cells.

2012 ◽  
Vol 9 (1) ◽  
pp. 23-30
Author(s):  
Baghdad Science Journal
Keyword(s):  
Immune Response ◽  
Red Blood Cells ◽  
Skin Test ◽  
Blood Cells ◽  
Cellular Immune Response ◽  
Leishmania Donovani ◽  
Cellular Immune ◽  
And Control ◽  
Delayed Type Of Hypersensitivity

The Evaluation of the immune response in Golden Hamsters experimentally infected with Leishmania donovani was determined in this study, particularly, the cellular immune response. Follow up has maintained to determine the Delayed Type of Hypersensitivity using skin test both in infected and control lab animals. Chicken red blood cells were used as a parameter to evaluate the immune system; they are dull and have the ability of immunization. Two concentrations of chicken R.B.C were examined to determine which gives the higher titration in Hamsters and those were 1.5 X 109 cell/ml and 3 X 109 cell/ml , the second concentration gave the maximum titration where then used in this work. After sensitization with Chicken R.B.C for both infected and control groups, delayed type of hypersensitivity has been used against Leishmania donovani antigen and 4 days of follow up were adopted and they were (14, 30, 60, 90) day after infection. Results showed that skin test against both antigens ( L.donovani and chicken R.B.C) was significantly higher than normal at the first day of follow up ( day 14) then gradual decreasing were noticed till the last day of follow up (90). This can indicate that the infection with L.donovani activated the immune response at the beginning of infection, then leads to cellular immune suppression against both L.donovani antigen and chicken R.B.C., so that this immunosuppression is not specific.

scholarly journals IFN-I Independent Antiviral Immune Response to Vesicular Stomatitis Virus Challenge in Mouse Brain

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 326
Author(s):  
Anurag R. Mishra ◽  
Siddappa N. Byrareddy ◽  
Debasis Nayak
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Vesicular Stomatitis Virus ◽  
Antiviral Response ◽  
Type I ◽  
Immune Gene ◽  
Antiviral Immune Response ◽  
Virus Challenge ◽  
Vesicular Stomatitis ◽  
Ifn Γ

Type I interferon (IFN-I) plays a pivotal role during viral infection response in the central nervous system (CNS). The IFN-I can orchestrate and regulate most of the innate immune gene expression and myeloid cell dynamics following a noncytopathic virus infection. However, the role of IFN-I in the CNS against viral encephalitis is not entirely clear. Here we have implemented the combination of global differential gene expression profiling followed by bioinformatics analysis to decipher the CNS immune response in the presence and absence of the IFN-I signaling. We observed that vesicular stomatitis virus (VSV) infection induced 281 gene changes in wild-type (WT) mice primarily associated with IFN-I signaling. This was accompanied by an increase in antiviral response through leukocyte vascular patrolling and leukocyte influx along with the expression of potent antiviral factors. Surprisingly, in the absence of the IFN-I signaling (IFNAR−/− mice), a significantly higher (1357) number of genes showed differential expression compared to the WT mice. Critical candidates such as IFN-γ, CCL5, CXCL10, and IRF1, which are responsible for the recruitment of the patrolling leukocytes, are also upregulated in the absence of IFN-I signaling. The computational network analysis suggests the presence of the IFN-I independent pathway that compensates for the lack of IFN-I signaling in the brain. The analysis shows that TNF-α is connected maximally to the networked candidates, thus emerging as a key regulator of gene expression and recruitment of myeloid cells to mount antiviral action. This pathway could potentiate IFN-γ release; thereby, synergistically activating IRF1-dependent ISG expression and antiviral response.

Sympathetic immunoregulation: difference between high- and low-responder animals

1982 ◽  
Vol 242 (1) ◽  
pp. R30-R33 ◽  
Author(s):  
A. del Rey ◽  
H. O. Besedovsky ◽  
E. Sorkin ◽  
M. Da Prada ◽  
G. P. Bondiolotti
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Quantitative Relationship ◽  
Spleen Weight ◽  
Low Responder ◽  
Sympathetic Nervous ◽  
High Responders

A quantitative relationship is reported between the magnitude of the immune response of rats to sheep red blood cells and diminution of splenic norepinephrine (NE). A decrease in concentration and content of NE in the spleen on day 3 after immunization was evident in both high- and low-responder animals, whereas a diminished concentration of NE persisted only in the high responders. This continuing NE diminution in high-responder animals is associated with increase in spleen weight, probably attributable to blood accumulation. These findings are consonant with the concept that the sympathetic nervous system is involved in immunoregulation.

scholarly journals miR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Jikai Zhang ◽  
Zhijie Li ◽  
Jiapei Huang ◽  
Hang Yin ◽  
Jin Tian ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Antiviral Response ◽  
Innate Immune ◽  
Host Cells ◽  
Type I ◽  
Type I Ifn ◽  
Feline Herpesvirus ◽  
Herpesvirus 1

In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling.

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