scholarly journals A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Micah T. McClain ◽  
Bradly P. Nicholson ◽  
Lawrence P. Park ◽  
Tzu-Yu Liu ◽  
Alfred O. Hero ◽  
...  
Keyword(s):  
Influenza Infection ◽  
Interferon Γ ◽  
Response To Therapy ◽  
Clinical Disease ◽  
Therapeutic Interventions ◽  
Genomic Signature ◽  
Early Therapy ◽  
Infectious Dose ◽  
Viral Shedding ◽  
Factor Α

Abstract Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid resolution of clinical disease (20 hours earlier), reduced viral shedding (total median tissue culture infectious dose [TCID50] 7.4 vs 9.7), and significantly reduced expression of several inflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin-6, and others). The host genomic response to influenza infection is robust and may provide the means for early detection, more timely therapeutic interventions, a meaningful reduction in clinical disease, and an effective molecular means to track response to therapy.

scholarly journals Cell Culture-Derived Tilapia Lake Virus-Inactivated Vaccine Containing Montanide Adjuvant Provides High Protection against Viral Challenge for Tilapia

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 86
Author(s):  
Weiwei Zeng ◽  
Yingying Wang ◽  
Huzi Hu ◽  
Qing Wang ◽  
Sven M. Bergmann ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Interferon Γ ◽  
Economic Losses ◽  
Mrna Levels ◽  
Infectious Dose ◽  
Booster Immunization ◽  
Virus Challenge ◽  
High Level ◽  
Factor Α

Tilapia lake virus (TiLV) is a newly emerging pathogen responsible for high mortality and economic losses in the global tilapia industry. Currently, no antiviral therapy or vaccines are available for the control of this disease. The goal of the present study was to evaluate the immunological effects and protective efficacy of formaldehyde- and β-propiolactone-inactivated vaccines against TiLV in the presence and absence of the Montanide IMS 1312 VG adjuvant in tilapia. We found that β-propiolactone inactivation of viral particles generated a vaccine with a higher protection efficacy against virus challenge than did formaldehyde. The relative percent survivals of vaccinated fish at doses of 108, 107, and 106 50% tissue culture infectious dose (TCID50)/mL were 42.9%, 28.5%, and 14.3% in the absence of the adjuvant and 85.7%, 64.3%, and 32.1% in its presence, respectively. The vaccine generated specific IgM and neutralizing antibodies against TiLV at 3 weeks following immunization that were significantly increased after a second booster immunization. The steady state mRNA levels of the genes tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon γ (IFN-γ), cluster of differentiation 4 (CD4), major histocompatibility complex (MHC)-Ia, and MHC-II were all increased and indicated successful immune stimulation against TiLV. The vaccine also significantly lowered the viral loads and resulted in significant increases in survival, indicating that the vaccine may also inhibit viral proliferation as well as stimulate a protective antibody response. The β-propiolactone-inactivated TiLV vaccine coupled with the adjuvant Montanide IMS 1312 VG and booster immunizations can provide a high level of protection from virus challenge in tilapia.

scholarly journals UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages

2020 ◽  
Vol 118 (1) ◽  
pp. e2011763118
Author(s):  
Dale R. Balce ◽  
Ya-Ting Wang ◽  
Michael R. McAllaster ◽  
Bria F. Dunlap ◽  
Anthony Orvedahl ◽  
...  
Keyword(s):  
Stress Responses ◽  
Influenza Infection ◽  
Interferon Γ ◽  
Conjugation System ◽  
Transcriptional Responses ◽  
Inhibitory Mechanisms ◽  
A Genome ◽  
Ifn Γ ◽  
Factor Α

Macrophages activated with interferon-γ (IFN-γ) in combination with other proinflammatory stimuli, such as lipopolysaccharide or tumor necrosis factor-α (TNF-α), respond with transcriptional and cellular changes that enhance clearance of intracellular pathogens at the risk of damaging tissues. IFN-γ effects must therefore be carefully balanced with inhibitory mechanisms to prevent immunopathology. We performed a genome-wide CRISPR knockout screen in a macrophage cell line to identify negative regulators of IFN-γ responses. We discovered an unexpected role of the ubiquitin-fold modifier (Ufm1) conjugation system (herein UFMylation) in inhibiting responses to IFN-γ and lipopolysaccharide. Enhanced IFN-γ activation in UFMylation-deficient cells resulted in increased transcriptional responses to IFN-γ in a manner dependent on endoplasmic reticulum stress responses involving Ern1 and Xbp1. Furthermore, UFMylation in myeloid cells is required for resistance to influenza infection in mice, indicating that this pathway modulates in vivo responses to infection. These findings provide a genetic roadmap for the regulation of responses to a key mediator of cellular immunity and identify a molecular link between the UFMylation pathway and immune responses.

scholarly journals Activation of autophagy reverses gemcitabine-induced immune inhibition of RAW264.7 macrophages by promoting TNF-α, IL-6 and MHC-II expression

2021 ◽  
Author(s):  
Shanshan Jiang ◽  
Rong Wang ◽  
Lu Han ◽  
Kudelaidi Kuerban ◽  
Li Ye ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Interferon Γ ◽  
Mhc Ii ◽  
Western Blot Method ◽  
Raw264.7 Macrophages ◽  
Histocompatibility Complex ◽  
Tnf Α ◽  
Factor Α ◽  
Cell Cycle Status ◽  
M1 Type

AbstractThis research aims to investigate the effect of gemcitabine (GEM) on various activities and functions of macrophages. Phagocytosis, cell autophagy and reactive oxygen species (ROS) were analysed by laser scanning confocal microscope. The cell cycle status and major histocompatibility complex II (MHC-II) expression were examined by flow cytometry. Inflammatory cytokine secretion such as tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) was detected by Elisa assay. The expression of proteins was analysed by western blot method. The results revealed that GEM-induced immune inhibition of M1-type RAW264.7 macrophages activated by interferon-γ (IFN-γ) and lipopolysaccharide (LPS). We also found that GEM inhibited autophagy, as evidenced by the reduced formation of autophagosome-like vacuoles and autophagosomes. Further study showed that incubation of activated macrophages with the autophagy inhibitor 3-MA induced immune suppression. In contrast, treatment with the autophagy inducer trehalose (Tre) restored phagocytosis, TNF-α and IL-6 secretion, and MHC-II expression in GEM-induced immune-inhibited macrophages. GEM reduced immune effect of M1-type RAW264.7 macrophages via inhibiting TNF-α, IL-6 and MHC-II expression. Furthermore, activation of autophagy by Tre reversed GEM-induced immune inhibition of RAW264.7 macrophages.

NK-dependent DC maturation is mediated by TNFα and IFNγ released upon engagement of the NKp30 triggering receptor

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 566-571 ◽  
Author(s):  
Massimo Vitale ◽  
Mariella Della Chiesa ◽  
Simona Carlomagno ◽  
Daniela Pende ◽  
Maurizio Aricò ◽  
...  
Keyword(s):  
Nk Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nk Cell ◽  
Interferon Γ ◽  
Cell Functions ◽  
Relevant Role ◽  
Factor Α ◽  
Necrosis Factor ◽  
Dc Maturation

Abstract Natural killer (NK) cells were recently shown to play a relevant role in the process of dendritic cell (DC) maturation. This function is exerted either by direct DC stimulation or through killing those DCs that did not properly acquire a mature phenotype. While killing of immature DCs is dependent on the function of the NKp30 triggering receptor, the mechanism by which NK cells induce DC maturation is still unclear. In this study, we show that also the NK-mediated induction of DC maturation is dependent on NKp30. Upon NK/DC interaction, resulting in NKp30 engagement, NK cells produced tumor necrosis factor α (TNFα) (and interferon γ [IFNγ]) that, in turn, promoted DC maturation. Masking of NKp30 with specific monoclonal antibodies (mAbs) strongly reduced maturation of DCs cocultured with NK cells. In addition, supernatant from NK cells stimulated via NKp30 induced DC maturation, and this effect was neutralized by anti-TNFα antibodies (Abs). This NKp30 function is controlled by the HLA-specific inhibitory NK receptors. Accordingly, the ability to promote maturation was essentially confined to NK cells expressing the killer immunoglobulin-like receptor–negative (KIR–) NKG2Adull phenotype. Finally, the analysis of perforin-deficient NK cells allowed the dissection of the 2 NKp30-mediated NK-cell functions, since NKp30 could induce cytokine-dependent DC maturation in the absence of NK-mediated DC killing.

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