A Blueprint for Cancer-Related Inflammation and Host Innate Immunity

Both in situ and allograft models of cancer in juvenile and adult Drosophila melanogaster fruit flies offer a powerful means for unravelling cancer gene networks and cancer–host interactions. They can also be used as tools for cost-effective drug discovery and repurposing. Moreover, in situ modeling of emerging tumors makes it possible to address cancer initiating events—a black box in cancer research, tackle the innate antitumor immune responses to incipient preneoplastic cells and recurrent growing tumors, and decipher the initiation and evolution of inflammation. These studies in Drosophila melanogaster can serve as a blueprint for studies in more complex organisms and help in the design of mechanism-based therapies for the individualized treatment of cancer diseases in humans. This review focuses on new discoveries in Drosophila related to the diverse innate immune responses to cancer-related inflammation and the systemic effects that are so detrimental to the host.

Download Full-text

Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

PLoS ONE ◽

10.1371/journal.pone.0015361 ◽

2011 ◽

Vol 6 (1) ◽

pp. e15361 ◽

Cited By ~ 21

Author(s):

Oana Marcu ◽

Matthew P. Lera ◽

Max E. Sanchez ◽

Edina Levic ◽

Laura A. Higgins ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses

Download Full-text

Meta-analysis of immune induced gene expression changes in diverse Drosophila melanogaster innate immune responses

10.1101/2021.09.23.461556 ◽

2021 ◽

Author(s):

Ashley L Waring ◽

Joshua Hill ◽

Brooke M Allen ◽

Nicholas M Bretz ◽

Nguyen Le ◽

...

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Immune Responses ◽

Meta Analysis ◽

Nuclear Factor Κb ◽

Innate Immune ◽

Innate Immune Responses ◽

Response Factors ◽

Induced Genes ◽

Conserved Gene

Background: Organisms are commonly infected by a diverse array of pathogen types including bacteria, fungi, viruses, and parasites, and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression in response to infection. However, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown. Results: We performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection. While many of these infection-induced genes encode known immune response factors, we also identified 21 genes that have not been previously associated with host immunity. Examination of the upstream flanking sequences of the infection-induced genes lead to the identification of two conserved enhancer sites. These sites correspond to conserved binding sites for GATA and nuclear factor κB (NFκB) family transcription factors and are associated with higher levels of transcript induction. We further identified 31 genes with predicted functions in metabolism and organismal development that are significantly downregulated following infection by diverse pathogens. Conclusions: Our study identifies conserved gene expression changes in Drosophila melanogaster following infection with varied pathogens, and transcription factor families that may regulate this immune induction. These findings provide new insight into transcriptional changes that accompany Drosophila immunity. They may suggest possible roles for the differentially regulated genes in innate immune responses to diverse classes of pathogens, and serve to identify candidate genes for further empirical study of these processes.

Download Full-text

Going further post-RNA-seq: In silico functional analyses revealing candidate genes and regulatory elements related to mastitis in dairy cattle

Journal of Dairy Research ◽

10.1017/s0022029921000571 ◽

2021 ◽

pp. 1-7

Author(s):

Hyago Passe Pereira ◽

Lucas Lima Verardo ◽

Mayara Morena Del Cambre Amaral Weller ◽

Ana Paula Sbardella ◽

Danísio Prado Munari ◽

...

Keyword(s):

Transcription Factors ◽

Immune Responses ◽

Streptococcus Agalactiae ◽

Gene Networks ◽

Regulatory Elements ◽

Innate Immune ◽

Innate Immune Responses ◽

Rna Seq ◽

Functional Analyses ◽

The Relationship

Abstract This study aimed to obtain a better understanding of the regulatory genes and molecules involved in the development of mastitis. For this purpose, the transcription factors (TF) and MicroRNAs (miRNA) related to differentially expressed genes previously found in extracorporeal udders infected with Streptococcus agalactiae were investigated. The Gene-TF network highlighted LOC515333, SAA3, CD14, NFKBIA, APOC2 and LOC100335608 and genes that encode the most representative transcription factors STAT3, PPARG, EGR1 and NFKB1 for infected udders. In addition, it was possible to highlight, through the analysis of the gene-miRNA network, genes that could be post-transcriptionally regulated by miRNAs, such as the relationship between the CCL5 gene and the miRNA bta-miR-363. Overall, our data demonstrated genes and regulatory elements (TF and miRNA) that can play an important role in mastitis resistance. The results provide new insights into the first functional pathways and the network of genes that orchestrate the innate immune responses to infection by Streptococcus agalactiae. Our results will increase the general knowledge about the gene networks, transcription factors and miRNAs involved in fighting intramammary infection and maintaining tissue during infection and thus enable a better understanding of the pathophysiology of mastitis.

Download Full-text

Hepatitis B Virus–Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms

Seminars in Liver Disease ◽

10.1055/s-0039-1685518 ◽

2019 ◽

Vol 39 (03) ◽

pp. 301-314 ◽

Cited By ~ 1

Author(s):

Emmanuel Thomas ◽

Thomas F. Baumert

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Immune Responses ◽

Viral Infection ◽

Signaling Pathways ◽

Viral Pathogenesis ◽

Innate Immune ◽

Innate Immune Responses ◽

Host Interactions ◽

B Virus

AbstractChronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide. While current therapeutic approaches can efficiently control viral infection, efficient curative antivirals are absent. The understanding of virus–hepatocyte interactions and sensing of viral infection is an important prerequisite for the development of novel antiviral therapies for cure. Hepatocyte intrinsic innate immunity provides a rapid first line of defense to combat viral infection through the upregulation of antiviral and inflammatory genes. However, the functional relevance of many of these antiviral signaling pathways in the liver and their role in HBV pathogenesis is still only partially understood. The recent identification of intracellular RNA and DNA sensing pathways and their involvement in disease biology, including viral pathogenesis and carcinogenesis, is currently transforming our understanding of virus–host interactions. Here the authors review the current knowledge on intrinsic antiviral innate immune responses including the role of viral nucleic acid sensing pathways in the liver. Since HBV has been designated as a “stealth virus,” the study of the impact of HBV on signaling pathways in the hepatocyte is of significant interest to understand viral pathogenesis. Characterizing the mechanism underlying these HBV–host interactions and targeting related pathways to enhance antiviral innate responses may open new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with chronic HBV infection.

Download Full-text

Immunity and Viral Infections: Modulating Antiviral Response via CRISPR–Cas Systems

Viruses ◽

10.3390/v13071373 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1373

Author(s):

Sergey Brezgin ◽

Anastasiya Kostyusheva ◽

Ekaterina Bayurova ◽

Elena Volchkova ◽

Vladimir Gegechkori ◽

...

Keyword(s):

Infectious Diseases ◽

Immune Responses ◽

Viral Infections ◽

Antiviral Agents ◽

Innate Immune ◽

Host Factors ◽

Innate Immune Responses ◽

Host Interactions ◽

Translational Studies ◽

Short Time

Viral infections cause a variety of acute and chronic human diseases, sometimes resulting in small local outbreaks, or in some cases spreading across the globe and leading to global pandemics. Understanding and exploiting virus–host interactions is instrumental for identifying host factors involved in viral replication, developing effective antiviral agents, and mitigating the severity of virus-borne infectious diseases. The diversity of CRISPR systems and CRISPR-based tools enables the specific modulation of innate immune responses and has contributed impressively to the fields of virology and immunology in a very short time. In this review, we describe the most recent advances in the use of CRISPR systems for basic and translational studies of virus–host interactions.

Download Full-text

Severe Acute Respiratory Syndrome Coronavirus Papain-Like Protease Ubiquitin-Like Domain and Catalytic Domain Regulate Antagonism of IRF3 and NF-κB Signaling

Journal of Virology ◽

10.1128/jvi.02220-08 ◽

2009 ◽

Vol 83 (13) ◽

pp. 6689-6705 ◽

Cited By ~ 181

Author(s):

Matthew Frieman ◽

Kiira Ratia ◽

Robert E. Johnston ◽

Andrew D. Mesecar ◽

Ralph S. Baric

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Immune Responses ◽

Catalytic Domain ◽

Innate Immune ◽

Signaling Proteins ◽

Accessory Proteins ◽

Innate Immune Responses ◽

Potential Mechanism ◽

Host Interactions ◽

Complex Coordination

ABSTRACT The outcome of a viral infection is regulated in part by the complex coordination of viral and host interactions that compete for the control and optimization of virus replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) intimately engages and regulates the host innate immune responses during infection. Using a novel interferon (IFN) antagonism screen, we show that the SARS-CoV proteome contains several replicase, structural, and accessory proteins that antagonize the IFN pathway. In this study, we focus on the SARS-CoV papain-like protease (PLP), which engages and antagonizes the IFN induction and NF-κB signaling pathways. PLP blocks these pathways by affecting activation of the important signaling proteins in each pathway, IRF3 and NF-κB. We also show that the ubiquitin-like domain of PLP is necessary for pathway antagonism but not sufficient by itself to block these pathways regardless of the enzymatic activity of the protease. The potential mechanism of PLP antagonism and its role in pathogenesis are discussed.

Download Full-text

Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

Download Full-text