scholarly journals Long noncoding RNAAVANpromotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a

2019 ◽  
Author(s):  
Chengcai Lai ◽  
Lihui Liu ◽  
Qinghua Liu ◽  
Sijie Cheng ◽  
Keyu Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Virus Production ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Forkhead Box ◽  
Innate Immune Signaling ◽  
Promising Target ◽  
Antiviral Innate Immunity

AbstractAccumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely unexplored. Here, we identify an uncharacterized human lncRNA from influenza A virus (IAV) patients, antivirus and activate neutrophil (AVAN), that is significantly up-regulated upon virus infection. Mechanistically, nuclear lncRNA-AVANpositively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Furthermore, we also found that cytoplasmic lncRNA-AVANdirectly binds tripartite motif containing 25 (TRIM25) and enhances the association of TRIM25 and Retinoic acid inducible gene-1 proteins (RIG-I) and the ubiquitylation of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune signaling. More importantly, we enforced the expression of AVAN in transgenic mice and found that it significantly alleviated IAV virulence and virus production. Collectively, these findings highlight the potential clinical implications of lncRNA-AVANas a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics.

scholarly journals Intestinal macrophages in mucosal immunity and their role in systemic lupus erythematosus disease

Lupus ◽  
2018 ◽  
Vol 27 (12) ◽  
pp. 1898-1902 ◽  
Author(s):  
F Pan ◽  
W Tang ◽  
Z Zhou ◽  
G Gilkeson ◽  
R Lang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Responses ◽  
Lupus Erythematosus ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Systemic Lupus ◽  
Innate Immune Signaling ◽  
Immune Signaling Pathway

Monocytes play an important role in inducing host systemic immunity against invading pathogens and inflammatory responses. After activation, monocytes migrate to tissue sites, where they initiate both innate and adaptive immune responses, and become macrophages. Although mucosal macrophages produce inflammatory cytokines in response to pathogens, the perturbations in innate immune signaling pathway have been implicated in autoimmune diseases such as systemic lupus erythematosus (SLE). In this review, we focus on the role of human macrophages in intestinal innate immune responses, homeostasis, and SLE disease. We further discuss sex differences in the intestinal macrophages and their role in the physiology and pathogenesis of SLE.

scholarly journals Innate Immune Sensing of Influenza A Virus

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 755
Author(s):  
Gaurav Malik ◽  
Yan Zhou
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Pyrin Domain ◽  
Immune Sensing ◽  
Influenza Viral Infection

Influenza virus infection triggers host innate immune response by stimulating various pattern recognition receptors (PRRs). Activation of these PRRs leads to the activation of a plethora of signaling pathways, resulting in the production of interferon (IFN) and proinflammatory cytokines, followed by the expression of interferon-stimulated genes (ISGs), the recruitment of innate immune cells, or the activation of programmed cell death. All these antiviral approaches collectively restrict viral replication inside the host. However, influenza virus also engages in multiple mechanisms to subvert the innate immune responses. In this review, we discuss the role of PRRs such as Toll-like receptors (TLRs), Retinoic acid-inducible gene I (RIG-I), NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3), and Z-DNA binding protein 1 (ZBP1) in sensing and restricting influenza viral infection. Further, we also discuss the mechanisms influenza virus utilizes, especially the role of viral non-structure proteins NS1, PB1-F2, and PA-X, to evade the host innate immune responses.

scholarly journals Effects and Side Effects of Platelet Transfusion

2021 ◽  
Author(s):  
Fabrice Cognasse ◽  
Kathryn Hally ◽  
Sebastien Fauteux-Daniel ◽  
Marie-Ange Eyraud ◽  
Charles-Antoine Arthaud ◽  
...  
Keyword(s):  
Side Effects ◽  
Immune Responses ◽  
Platelet Transfusion ◽  
Biological Response ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Stress Injury ◽  
Processing And Storage ◽  
And Storage

AbstractAside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage. With these types of stress, they undergo morphologic, metabolic, and functional modulations which are likely to induce platelet activation and the release of biological response modifiers (BRMs). As a consequence, platelet concentrates (PCs) accumulate BRMs during processing and storage, and these BRMs are ultimately transfused alongside platelets. It has been shown that BRMs present in PCs can induce immune responses and posttransfusion reactions in the transfusion recipient. Several recent reports within the transfusion literature have investigated the concept of platelets as immune cells. Nevertheless, current and future investigations will face the challenge of encompassing the immunological role of platelets in the scope of transfusion.

scholarly journals Emerging Roles of Protein Deamidation in Innate Immune Signaling

2016 ◽  
Vol 90 (9) ◽  
pp. 4262-4268 ◽  
Author(s):  
Jun Zhao ◽  
Junhua Li ◽  
Simin Xu ◽  
Pinghui Feng
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Biological Processes ◽  
Innate Immune Responses ◽  
Immune Signaling ◽  
Host Immune Responses ◽  
Innate Immune Signaling ◽  
Enzyme Deficient ◽  
Signaling Components

Protein deamidation has been considered a nonenzymatic process associated with protein functional decay or “aging.” Recent studies implicate protein deamidation in regulating signal transduction in fundamental biological processes, such as innate immune responses. Work investigating gammaherpesviruses and bacterial pathogens indicates that microbial pathogens deploy deamidases or enzyme-deficient homologues (pseudoenzymes) to induce deamidation of key signaling components and evade host immune responses. Here, we review studies on protein deamidation in innate immune signaling and present several imminent questions concerning the roles of protein deamidation in infection and immunity.

scholarly journals Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 708 ◽  
Author(s):  
Aitor Nogales ◽  
Luis Martinez-Sobrido ◽  
David Topham ◽  
Marta DeDiego
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Defense Mechanisms ◽  
Synergistic Effects ◽  
Viral Proteins ◽  
Economic Problem ◽  
Innate Immune ◽  
Host Protein ◽  
Innate Immune Responses ◽  
Influenza A Viruses

Influenza A viruses (IAV) can infect a broad range of animal hosts, including humans. In humans, IAV causes seasonal annual epidemics and occasional pandemics, representing a serious public health and economic problem, which is most effectively prevented through vaccination. The defense mechanisms that the host innate immune system provides restrict IAV replication and infection. Consequently, to successfully replicate in interferon (IFN)-competent systems, IAV has to counteract host antiviral activities, mainly the production of IFN and the activities of IFN-induced host proteins that inhibit virus replication. The IAV multifunctional proteins PA-X and NS1 are virulence factors that modulate the innate immune response and virus pathogenicity. Notably, these two viral proteins have synergistic effects in the inhibition of host protein synthesis in infected cells, although using different mechanisms of action. Moreover, the control of innate immune responses by the IAV NS1 and PA-X proteins is subject to a balance that can determine virus pathogenesis and fitness, and recent evidence shows co-evolution of these proteins in seasonal viruses, indicating that they should be monitored for enhanced virulence. Importantly, inhibition of host gene expression by the influenza NS1 and/or PA-X proteins could be explored to develop improved live-attenuated influenza vaccines (LAIV) by modulating the ability of the virus to counteract antiviral host responses. Likewise, both viral proteins represent a reasonable target for the development of new antivirals for the control of IAV infections. In this review, we summarize the role of IAV NS1 and PA-X in controlling the antiviral response during viral infection.

scholarly journals Ironing Out the Details: How Iron Orchestrates Macrophage Polarization

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaoyao Xia ◽  
Yikun Li ◽  
Xiaoyan Wu ◽  
Qingzhuo Zhang ◽  
Siyuan Chen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Immune Responses ◽  
Epigenetic Regulation ◽  
Crucial Role ◽  
Liver Diseases ◽  
Iron Supplementation ◽  
Macrophage Polarization ◽  
Innate Immune ◽  
Innate Immune Responses

Iron fine-tunes innate immune responses, including macrophage inflammation. In this review, we summarize the current understanding about the iron in dictating macrophage polarization. Mechanistically, iron orchestrates macrophage polarization through several aspects, including cellular signaling, cellular metabolism, and epigenetic regulation. Therefore, iron modulates the development and progression of multiple macrophage-associated diseases, such as cancer, atherosclerosis, and liver diseases. Collectively, this review highlights the crucial role of iron for macrophage polarization, and indicates the potential application of iron supplementation as an adjuvant therapy in different inflammatory disorders relative to the balance of macrophage polarization.

scholarly journals The microbiota plays a critical role in the reactivity of lung immune components to innate ligands

2020 ◽  
Author(s):  
Quentin Marquant ◽  
Daphné Laubreton ◽  
Carole Drajac ◽  
Elliot Mathieu ◽  
Edwige Bouguyon ◽  
...  
Keyword(s):  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Immune Reactivity ◽  
Innate Immune Responses ◽  
Plain Language ◽  
Pulmonary Tissue ◽  
Germ Free ◽  
Syncytial Virus

AbstractThe microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota can modulate reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific pathogen-free (SPF) and germ-free (GF) mice. Using SPF and GF mice intranasally exposed to lipopolysaccharide (LPS), a component of Gram-negative bacteria, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice. Toll-like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.Plain Language summaryMicrobiota represents an important partner of immunologic system at the interface between immune cells and epithelium. It is well known, notably in the gut, that the microbiota contributes in shaping efficient and safe defenses. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. In this study, we postulate that endogenous microbiota could dampen an excessive reactivity of pulmonary tissue to external stimuli. Thus, we sought to study the innate immune reaction switched on by viral or bacterial ligands in respiratory tract cells coming from mice with or without microbiota (germ-free condition, GF). Altogether, our results show a higher inflammatory reaction in GF condition. This study represents a step forward to better establish the link between the microbiota and the reactivity of the lung tissue. Not only these data demonstrate that the microbiota educates the pulmonary innate immune system, but also contributes the emerging concept of using respiratory commensal bacteria as potential next-generation probiotics to prevent susceptibility to respiratory diseases.

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