scholarly journals IL-6 signalling protects zebrafish larvae during Staphylococcus epidermidis infection in a novel bath immersion model

2020 ◽  
Author(s):  
PT Dhanagovind ◽  
Prabeer K. Kujur ◽  
Rajeeb K. Swain ◽  
Sanjita Banerjee
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Staphylococcus Epidermidis ◽  
Signalling Pathway ◽  
Infection Model ◽  
Primary Role ◽  
Signal Transducer ◽  
Host Immune Responses ◽  
Zebrafish Larvae ◽  
Pro Inflammatory Cytokines

AbstractHost immune responses to Staphylococcus epidermidis, a frequent cause of nosocomial infections, are not well understood. We have established a novel bath immersion model of this infection in zebrafish larvae. S.epidermidis infection activates Tlr-2 signalling pathway by upregulation of tlr-2. Macrophages play a primary role in the host immune response and are involved in clearance of infection in the larvae. There is marked inflammation characterised by heightened NF-κB signalling and elevation of several pro-inflammatory cytokines. Infected larvae show rapid upregulation of il-1b and tnf-a transcripts and relatively slower elevation of il-6 transcription. The IL-6 signalling pathway is additionally subject to amplification by elevation of IL-6 signal transducer (il-6st) levels, which negatively correlates with miRNA dre-miR-142-5p expression. Enhanced IL-6 signalling is protective to the host in this model as inhibition of the signalling pathway resulted in increased mortality upon S.epidermidis infection. Our study describes the host immune responses to S.epidermidis infection, identifies a likely role for miR-142-5p – il-6st interaction in modulating this response and establishes the importance of IL-6 signalling in this infection model.

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 Extracellular Vesicles from Different Pneumococcal Serotypes Are Internalized by Macrophages and Induce Host Immune Responses

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1530
Author(s):  
Alfonso Olaya-Abril ◽  
Rafael Prados-Rosales ◽  
José A. González-Reyes ◽  
Arturo Casadevall ◽  
Liise-anne Pirofski ◽  
...  
Keyword(s):  
Immune Response ◽  
Biological Activity ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Host Cells ◽  
Pneumococcal Serotypes ◽  
Human Pathogen ◽  
Host Immune Responses ◽  
Serotype 1 ◽  
Transient Loss

Bacterial extracellular vesicles are membranous ultrastructures released from the cell surface. They play important roles in the interaction between the host and the bacteria. In this work, we show how extracellular vesicles produced by four different serotypes of the important human pathogen, Streptococcus pneumoniae, are internalized by murine J774A.1 macrophages via fusion with the membrane of the host cells. We also evaluated the capacity of pneumococcal extracellular vesicles to elicit an immune response by macrophages. Macrophages treated with the vesicles underwent a serotype-dependent transient loss of viability, which was further reverted. The vesicles induced the production of proinflammatory cytokines, which was higher for serotype 1 and serotype 8-derived vesicles. These results demonstrate the biological activity of extracellular vesicles of clinically important pneumococcal serotypes.

scholarly journals Viremia in Equine Herpes Virus-1 infection and a possible link to Transient Protective Immunity

2021 ◽  
Vol 9 (1) ◽  
pp. 11-16
Author(s):  
AR Awan ◽  
OL Tulp ◽  
HJ Field
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Murine Model ◽  
Herpes Virus ◽  
Natural Infection ◽  
Fluorescent Antibody ◽  
Buffy Coat ◽  
Effective Vaccine ◽  
Infection Model ◽  
Herpès Virus

Equine herpes virus (EHV-1) causes respiratory infections in equine, and results in abortion, paresis, neonatal death, and retinopathy and the virus may become latent following initial infection. Virus entry is via the respiratory route, and the virus replicates in the host in ciliated and non-ciliated epithelial cells of the respiratory tract and in Type 1 and Type 2 pneumocytes in the lung parenchyma. After viral replication in the respiratory system, the virus can become disseminated to other parts of body via viraemic cells. The virus also can cross the placenta which leads to abortion of live or dead fetuses without premonitory signs. Infected horses show transient immunity after natural or experimental infection and immune responses to EHV-1, but the immunoprotective status begins to decline after a few months of active infection. Due to the transient immune response, recovered horses are not immunoprotected and thus are prone to subsequent re-infection. Immunity is not long lived after experimental or natural infection, and as a result the development of an effective vaccine has remained a challenge. In this study viraemic cells were studied in a murine EHV-1 infection model. Mice were infected intranasally and viraemic cells were studied on days three and five which occurs during the peak of the infection. The results of this study may help to identify the nature of viraemic cells and their role in the transient immune response to infection. Buffy coat cells and lungs were removed and stained with a fluorescent antibody test for EHV-1 antigen, and lung specimens were subjected to transmission electron microscopy. Both techniques confirmed the presence of viraemic cells in lung tissues. These viraemic cells were further stained for EHV-1 antigen, and for CD4 or CD8 biomarkers and results are discussed re: pathogenesis of EHV-1 infection, identification of viraemic cells in a murine model and possible link of viraemia to transient immune responses in EHV-1 infection, which demonstrate the validity of this murine model for the investigation of the cytopathologic mechanism and sequelae of EHV manifestation in this model.

scholarly journals The Sp1-Responsive microRNA-15b Negatively Regulates Rhabdovirus-Triggered Innate Immune Responses in Lower Vertebrates by Targeting TBK1

2021 ◽  
Vol 11 ◽  
Author(s):  
Renjie Chang ◽  
Qing Chu ◽  
Weiwei Zheng ◽  
Lei Zhang ◽  
Tianjun Xu
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune ◽  
Infection Model ◽  
Regulation Mechanism ◽  
Type I ◽  
Innate Immune Responses ◽  
Positive Role ◽  
Siniperca Chuatsi ◽  
Antiviral Immune Response

As is known to all, the production of type I interferon (IFN) plays pivotal roles in host innate antiviral immunity, and its moderate production play a positive role in promoting the activation of host innate antiviral immune response. However, the virus will establish a persistent infection model by interfering with the production of IFN, thereby evading the organism inherent antiviral immune response. Therefore, it is of great necessity to research the underlying regulatory mechanisms of type I IFN appropriate production under viral invasion. In this study, we report that a Sp1–responsive miR-15b plays a negative role in siniperca chuatsi rhabdovirus (SCRV)-triggered antiviral response in teleost fish. We found that SCRV could dramatically upregulate miiuy croaker miR-15b expression. Enhanced miR-15b could negatively regulate SCRV-triggered antiviral genes and inflammatory cytokines production by targeting TANK-binding kinase 1 (TBK1), thereby accelerating viral replication. Importantly, we found that miR-15b feedback regulates antiviral innate immune response through NF-κB and IRF3 signaling pathways. These findings highlight that miR-15b plays a crucial role in regulating virus–host interactions, which outlines a new regulation mechanism of fish’s innate immune responses.

scholarly journals Protective and Pathogenic Immune Responses to Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Elina Panahi ◽  
Danielle I. Stanisic ◽  
Christopher S. Peacock ◽  
Lara J. Herrero
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cutaneous Leishmaniasis ◽  
Adaptive Immune Response ◽  
Leishmania Parasite ◽  
Host Immune System ◽  
Phagocytic Cells ◽  
Host Immune Responses ◽  
Outcome Severity ◽  
Common Clinical Presentation

Leishmania (Kinetoplastida: Trypanosomatidae) parasites are known to cause a broad spectrum of clinical diseases in humans, collectively known as the leishmaniases. Cutaneous leishmaniasis is the most common clinical presentation with varying degrees of severity largely driven by host immune responses, specifically the interplay between innate and adaptive immune response. The establishment of a T lymphocyte driven cell-mediated immune response, leading to activated phagocytic cells, leading to Leishmania parasite killing and control of infection. Alternatively, the Leishmania parasite manipulates the host immune system, enabling parasite proliferation and clinical disease. Here we review how the cumulative interactions of different aspects of the host immune response determines disease outcome, severity, and immunity to re-infection.

scholarly journals Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

2020 ◽  
Author(s):  
Yapeng Su ◽  
Daniel Chen ◽  
Christopher Lausted ◽  
Dan Yuan ◽  
Jongchan Choi ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Surface Proteins ◽  
Host Immune Responses ◽  
Therapeutic Development ◽  
Clinical Measures ◽  
Whole Transcriptome

SUMMARYHost immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.

scholarly journals Host Immune Response and Novel Diagnostic Approach to NTM Infections

2020 ◽  
Vol 21 (12) ◽  
pp. 4351
Author(s):  
Yuko Abe ◽  
Kiyoharu Fukushima ◽  
Yuki Hosono ◽  
Yuki Matsumoto ◽  
Daisuke Motooka ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Diagnostic Approach ◽  
Post Transplantation ◽  
Diagnosis And Management ◽  
Immunological Responses ◽  
Host Immune Responses ◽  
Diagnostic Approaches ◽  
Proper Diagnosis

The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species.

scholarly journals Infection, Inflammation and Immunity in Covid-19 Infection

2021 ◽  
Vol 48 (3) ◽  
pp. 77-82
Author(s):  
R. Cherneva ◽  
Z. Cherneva
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Immune Responses ◽  
Systemic Inflammation ◽  
Multiple Organ ◽  
Host Immunity ◽  
Effective Prevention ◽  
Systemic Complications ◽  
Host Immune Responses ◽  
Prevention And Treatment

Abstract The COVID-19 pandemic caused by the SARS-CoV-2 has increased the burden on healthcare system. Despite some progress in its diagnostics has been made, effective prevention and treatment are still insufficient. Since SARS-CoV-2 infections often cause systemic inflammation and multiple organ failure, the therapeutic options aimed at modulating the host immune responses to prevent subsequent systemic complications are demanding. The review provides a summary of the SARS-CoV-2 virus infection and underlines the current perception of pulmonary host’s immune response and its contributions to disease severity and systemic inflammation. Signaling pathways which have the potential to manipulate host immunity and improve clinical outcomes are also presented.

Electroacupuncture regulates the DREAM/NF-κB signalling pathway and ameliorates cyclophosphamide-induced immunosuppression in mice

2019 ◽  
Vol 37 (5) ◽  
pp. 292-300
Author(s):  
Zhihua Huang ◽  
Zhiping Hu ◽  
Juan Ouyang ◽  
Cheng Huang
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Regulatory Element ◽  
Interferon Γ ◽  
Signalling Pathway ◽  
Cell Toxicity ◽  
Immunosuppressed Patients ◽  
Factor Α ◽  
Immunosuppressed Mice

Background: Immune responses inhibit invasion by pathogens and antigens. Thus, it is important to promote the immune response in immunosuppressed patients. Objective: To examine whether electroacupuncture (EA) promotes the immune response by regulating the downstream regulatory element antagonist modulator / nuclear factor kappa B (DREAM/NF-κB) signalling pathway in a mouse model of cyclophosphamide (CP)-induced immunosuppression, and determine the most effective frequency. Methods: Twenty-four Kunming mice were intraperitoneally injected with CP to establish an immunosuppression model and six mice were injected with the same volume of normal saline as a control. The 24 mice were randomly divided into four groups: manual acupuncture, 2 Hz EA treatment, 100 Hz EA treatment and alternating 2/100 Hz EA treatment. After EA treatment for 3 days, immune response, natural killer (NK) cell toxicity and the expression of cytokines and DREAM/NF-κB were assessed. Results: EA treatment, especially at alternating 2/100 Hz frequency, improved spleen and thymus indices, increased lactate dehydrogenase and acid phosphatase levels, promoted concanavalin A- and lipopolysaccharide-induced splenocyte proliferation, increased NK cell toxicity and ameliorated CP-induced immunosuppression in mice. Additionally, 2/100 Hz EA treatment increased interleukin (IL)−2, IL-6, IL-12, tumour necrosis factor-α and interferon-γ levels and decreased IL-10 levels in CP-induced immunosuppressed mice. Finally, it was found that 2/100 Hz EA treatment increased p-IκBα and NF-κB expression and decreased DREAM and IκBα expression, suggesting that this treatment activates the NF-κB signalling pathway. Conclusion: 2/100 Hz EA treatment might be an effective way to enhance immune responses in CP-induced immunosuppressed mice.

scholarly journals Established Cotton Stainer Gut Bacterial Mutualists Evade Regulation by Host Antimicrobial Peptides

2019 ◽  
Vol 85 (13) ◽  
Author(s):  
Thomas Ogao Onchuru ◽  
Martin Kaltenpoth
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Target Genes ◽  
Quantitative Composition ◽  
Bacterial Symbionts ◽  
Immune Systems ◽  
Host Fitness ◽  
Host Immune Responses ◽  
Cotton Stainer ◽  
The Impact

ABSTRACT Symbioses with microorganisms are ubiquitous in nature and confer important ecological traits to animal hosts but also require control mechanisms to ensure homeostasis of the symbiotic interactions. In addition to protecting hosts against pathogens, animal immune systems recognize, respond to, and regulate mutualists. The gut bacterial symbionts of the cotton stainer bug, Dysdercus fasciatus, elicit an immune response characterized by the upregulation of c-type lysozyme and the antimicrobial peptide pyrrhocoricin in bugs with their native gut microbiota compared to that in dysbiotic insects. In this study, we investigated the impact of the elicited antimicrobial immune response on the established cotton stainer gut bacterial symbiont populations. To this end, we used RNA interference (RNAi) to knock down immunity-related genes hypothesized to regulate the symbionts, and we subsequently measured the effect of this silencing on host fitness and on the abundance of the major gut bacterial symbionts. Despite successful downregulation of target genes by both ingestion and injection of double-stranded RNA (dsRNA), the silencing of immunity-related genes had no effect on either host fitness or the qualitative and quantitative composition of established gut bacterial symbionts, indicating that the host immune responses are not actively involved in the regulation of the nutritional and defensive gut bacterial mutualists. These results suggest that close associations of bacterial symbionts with their hosts can result in the evolution of mechanisms ensuring that symbionts remain insensitive to host immunological responses, which may be important for the evolutionary stability of animal-microbe symbiotic associations. IMPORTANCE Animal immune systems are central for the protection of hosts against enemies by preventing or eliminating successful infections. However, in the presence of beneficial bacterial mutualists, the immune system must strike a balance of not killing the beneficial symbionts while at the same time preventing enemy attacks. Here, using the cotton stainer bug, we reveal that its long-term associated bacterial symbionts are insensitive to the host’s immune effectors, suggesting adaptation to the host’s defenses, thereby strengthening the stability of the symbiotic relationship. The ability of the symbionts to elicit host immune responses but remain insensitive themselves may be a mechanism by which the symbionts prime hosts to fight future pathogenic infections.

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