scholarly journals The Effects of In Vivo Exposure to Copper Oxide Nanoparticles on the Gut Microbiome, Host Immunity, and Susceptibility to a Bacterial Infection in Earthworms

Nanomaterials ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1337 ◽  
Author(s):  
Elmer Swart ◽  
Jiri Dvorak ◽  
Szabolcs Hernádi ◽  
Tim Goodall ◽  
Peter Kille ◽  
...  
Keyword(s):  
Immune Responses ◽  
Gut Microbiome ◽  
Methodological Approach ◽  
Copper Oxide Nanoparticles ◽  
Mrna Levels ◽  
Immune Genes ◽  
Host Immune Responses ◽  
Earthworm Gut ◽  
Bacterium Bacillus

Nanomaterials (NMs) can interact with the innate immunity of organisms. It remains, however, unclear whether these interactions can compromise the immune functioning of the host when faced with a disease threat. Co-exposure with pathogens is thus a powerful approach to assess the immuno-safety of NMs. In this paper, we studied the impacts of in vivo exposure to a biocidal NM on the gut microbiome, host immune responses, and susceptibility of the host to a bacterial challenge in an earthworm. Eisenia fetida were exposed to CuO-nanoparticles in soil for 28 days, after which the earthworms were challenged with the soil bacterium Bacillus subtilis. Immune responses were monitored by measuring mRNA levels of known earthworm immune genes. Effects of treatments on the gut microbiome were also assessed to link microbiome changes to immune responses. Treatments caused a shift in the earthworm gut microbiome. Despite these effects, no impacts of treatment on the expression of earthworm immune markers were recorded. The methodological approach applied in this paper provides a useful framework for improved assessment of immuno-safety of NMs. In addition, we highlight the need to investigate time as a factor in earthworm immune responses to NM exposure.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals How the gut microbiome regulates host immune responses to viral vaccines

2019 ◽  
Vol 37 ◽  
pp. 16-25 ◽  
Author(s):  
Anastasia N Vlasova ◽  
Sayaka Takanashi ◽  
Ayako Miyazaki ◽  
Gireesh Rajashekara ◽  
Linda J Saif
Keyword(s):  
Immune Responses ◽  
Gut Microbiome ◽  
Host Immune Responses ◽  
Viral Vaccines

scholarly journals Seroprevalence of Antibodies against Pkn1, a Novel Potential Immunogen, inChlamydia trachomatis-InfectedMacaca nemestrinaand Human Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Achchhe L. Patel ◽  
Prashant K. Mishra ◽  
Divya Sachdev ◽  
Uma Chaudhary ◽  
Dorothy L. Patton ◽  
...  
Keyword(s):  
Immune Responses ◽  
Genital Tract ◽  
Protein A ◽  
Macaca Nemestrina ◽  
Sexually Transmitted ◽  
Host Immune Responses ◽  
Bioinformatic Tools ◽  
Genital Tract Infections ◽  
Tract Infections

Chlamydia trachomatis(CT) is an important cause of sexually transmitted genital tract infections (STIs) and trachoma. Despite major research into chlamydial pathogenesis and host immune responses, immunoprotection has been hampered by the incomplete understanding of protective immunity in the genital tract. Characterized vaccine candidates have shown variable efficacy ranging from no protection to partial protectionin vivo. It is therefore a research priority to identify novel chlamydial antigens that may elicit protective immune responses against CT infection. In the present study we assessed the seroprevalence of antibodies against protein kinase1 (Pkn1), DNA ligaseA (LigA), and major outer membrane protein A (OmpA) following natural CT infection in humans and in experimentally induced CT infection inMacaca nemestrina. Antigenic stretches of Pkn1, LigA, and OmpA were identified using bioinformatic tools.Pkn1,LigA, andOmpAgenes were cloned in bacterial expression vector and purified by affinity chromatography. Our results demonstrate significantly high seroprevalence of antibodies against purified Pkn1 and OmpA in sera obtained from the macaque animal model and human patients infected with CT. In contrast no significant seroreactivity was observed for LigA. The seroprevalence of antibodies against Pkn1 suggest that nonsurface chlamydial proteins could also be important for developing vaccines forC. trachomatis.

scholarly journals Exaggerated in vivo IL-17 responses discriminate recall responses in active TB

2019 ◽  
Author(s):  
Gabriele Pollara ◽  
Carolin T Turner ◽  
Gillian S Tomlinson ◽  
Lucy CK Bell ◽  
Ayesha Khan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Th17 Cells ◽  
Latent Infection ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases ◽  
Host Immune Responses ◽  
Matrix Metalloproteinase 1 ◽  
First Time

AbstractHost immune responses at the site of Mycobacterium tuberculosis (Mtb) infection serve to contain the pathogen, but also mediate the pathogenesis of tuberculosis (TB) and onward transmission of infection. Interferon gamma (IFNγ) responses do not discriminate between protection and pathogenicity, but IL-17A/F responses, known to drive pathology in diverse chronic inflammatory diseases, have also been associated with TB pathogenesis in animal models. At the site of in vivo immune recall responses to Mtb modelled by the tuberculin skin test, we show for the first time that active TB in humans is also associated with exaggerated IL-17A/F expression, accumulation of Th17 cells and IL-17A/F bioactivity, including increased neutrophil recruitment and matrix metalloproteinase-1 expression directly implicated in TB pathogenesis. These features discriminate recall responses in patients with active TB from those with cured or latent infection and are also evident at the site of TB disease. Our data support targeting of this pathway in host-directed therapy for TB.

scholarly journals Helper-Dependent Adenovirus Vectors Elicit Intact Innate but Attenuated Adaptive Host Immune Responses In Vivo

2004 ◽  
Vol 78 (11) ◽  
pp. 5966-5972 ◽  
Author(s):  
Daniel A. Muruve ◽  
Matthew J. Cotter ◽  
Anne K. Zaiss ◽  
Lindsay R. White ◽  
Qiang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Second Phase ◽  
Liver Inflammation ◽  
Adaptive Immune Responses ◽  
Necrosis Factor Alpha ◽  
Host Immune Responses ◽  
Animal Models Of Disease ◽  
Adaptive Immune

ABSTRACT Helper-dependent adenovirus (HD-Ad) vectors with all adenoviral genes deleted mediate very long-term expression of therapeutic transgenes in a variety of animal models of disease. These vectors are associated with reduced toxicity and improved safety relative to traditional early region 1 deletion first-generation Ad (FG-Ad) vectors. Many studies have clearly demonstrated that FG-Ad vectors induce innate and adaptive immune responses in vivo; however, a comprehensive analysis of host immune responses to HD-Ad vectors has not yet been performed. In DBA/2 mice, intravenous injection of HD-Ad vectors encoding LacZ (HD-AdLacZ) or a murine secreted alkaline phosphatase (HD-AdSEAP) induced an early expression of inflammatory cytokine and chemokine genes in the liver, including interferon-inducible protein 10, macrophage inflammatory protein 2, and tumor necrosis factor alpha, and were expressed in a pattern similar to that induced by FG-Ad vectors encoding AdSEAP. Like AdSEAP, and consistent with the pattern of cellular gene expression, HD-AdLacZ and HD-AdSEAP induced the recruitment of CD11b-positive leukocytes to the transduced liver within hours of administration. AdSEAP also induced a second phase of liver inflammation, consisting of inflammatory gene expression and CD3-positive lymphocytic infiltrates 7 days posttransduction. In contrast, beyond 24 h no infiltrates or expression of inflammatory genes was detected in the livers of mice receiving HD-AdSEAP. Despite the lack of liver inflammation at 7 days, Ad-specific cytotoxic T lymphocytes could be detected in mice receiving HD-AdSEAP. This lack of liver inflammation was not due to reduced transduction since levels of transgene expression and the amounts of vector DNA in the liver were equivalent in mice receiving HD-AdSEAP and AdSEAP. These results demonstrate that HD-Ad vectors induce intact innate but attenuated adaptive immune responses in vivo.

scholarly journals The receptor-like kinase NIK1 targets FLS2/BAK1 immune complex and inversely modulates antiviral and antibacterial immunity

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Bo Li ◽  
Marco Aurélio Ferreira ◽  
Mengling Huang ◽  
Luiz Fernando Camargos ◽  
Xiao Yu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Regulatory Mechanism ◽  
Negative Regulator ◽  
Signal Transduction Pathways ◽  
Related Function ◽  
Host Immune Responses ◽  
Receptor Like Kinase ◽  
Important Negative Regulator ◽  
Simultaneous Infection

Abstract Plants deploy various immune receptors to recognize pathogens and defend themselves. Crosstalk may happen among receptor-mediated signal transduction pathways in the same host during simultaneous infection of different pathogens. However, the related function of the receptor-like kinases (RLKs) in thwarting different pathogens remains elusive. Here, we report that NIK1, which positively regulates plant antiviral immunity, acts as an important negative regulator of antibacterial immunity. nik1 plants exhibit dwarfed morphology, enhanced disease resistance to bacteria and increased PAMP-triggered immunity (PTI) responses, which are restored by NIK1 reintroduction. Additionally, NIK1 negatively regulates the formation of the FLS2/BAK1 complex. The interaction between NIK1 and FLS2/BAK1 is enhanced upon flg22 perception, revealing a novel PTI regulatory mechanism by an RLK. Furthermore, flg22 perception induces NIK1 and RPL10A phosphorylation in vivo, activating antiviral signalling. The NIK1-mediated inverse modulation of antiviral and antibacterial immunity may allow bacteria and viruses to activate host immune responses against each other.

scholarly journals GABA transporter sustains IL-1β production in macrophages

2021 ◽  
Vol 7 (15) ◽  
pp. eabe9274
Author(s):  
Yaoyao Xia ◽  
Fang He ◽  
Xiaoyan Wu ◽  
Bie Tan ◽  
Siyuan Chen ◽  
...  
Keyword(s):  
Immune Responses ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
High Fat ◽  
Gaba Transporter ◽  
Host Immune Responses ◽  
Diet Induced Obesity

Accumulating evidence shows that nervous system governs host immune responses; however, how γ-aminobutyric acid (GABA)ergic system shapes the function of innate immune cells is poorly defined. Here, we demonstrate that GABA transporter (GAT2) modulates the macrophage function. GAT2 deficiency lowers the production of interleukin-1β (IL-1β) in proinflammatory macrophages. Mechanistically, GAT2 deficiency boosts the betaine/S-adenosylmethionine (SAM)/hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through the increased DNA methylation in its promoter region. KID3 regulates oxidative phosphorylation (OXPHOS) via targeting the expression of OXPHOS-related genes and is also critical for NLRP3–ASC–caspase-1 complex formation. Likewise, GAT2 deficiency attenuates macrophage-mediated inflammatory responses in vivo, including lipopolysaccharide-induced sepsis, infection-induced pneumonia, and high-fat diet-induced obesity. Together, we propose that targeting GABAergic system (e.g., GABA transporter) could provide previously unidentified therapeutic opportunities for the macrophage-associated diseases.

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