Diversity of molecular mechanisms used by anti-CRISPR proteins: the tip of an iceberg?

Bacteriophages (phages) and their preys are engaged in an evolutionary arms race driving the co-adaptation of their attack and defense mechanisms. In this context, phages have evolved diverse anti-CRISPR proteins to evade the bacterial CRISPR–Cas immune system, and propagate. Anti-CRISPR proteins do not share much resemblance with each other and with proteins of known function, which raises intriguing questions particularly relating to their modes of action. In recent years, there have been many structure–function studies shedding light on different CRISPR–Cas inhibition strategies. As the anti-CRISPR field of research is rapidly growing, it is opportune to review the current knowledge on these proteins, with particular emphasis on the molecular strategies deployed to inactivate distinct steps of CRISPR–Cas immunity. Anti-CRISPR proteins can be orthosteric or allosteric inhibitors of CRISPR–Cas machineries, as well as enzymes that irreversibly modify CRISPR–Cas components. This repertoire of CRISPR–Cas inhibition mechanisms will likely expand in the future, providing fundamental knowledge on phage–bacteria interactions and offering great perspectives for the development of biotechnological tools to fine-tune CRISPR–Cas-based gene edition.

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NOD-Like Receptors: Guards of Cellular Homeostasis Perturbation during Infection

International Journal of Molecular Sciences ◽

10.3390/ijms22136714 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6714

Author(s):

Gang Pei ◽

Anca Dorhoi

Keyword(s):

Immune System ◽

Innate Immune System ◽

Current Knowledge ◽

Protein Translation ◽

Innate Immune ◽

Cellular Homeostasis ◽

Translation Block ◽

Cytoskeleton Disruption ◽

Molecular Patterns ◽

Fine Tune

The innate immune system relies on families of pattern recognition receptors (PRRs) that detect distinct conserved molecular motifs from microbes to initiate antimicrobial responses. Activation of PRRs triggers a series of signaling cascades, leading to the release of pro-inflammatory cytokines, chemokines and antimicrobials, thereby contributing to the early host defense against microbes and regulating adaptive immunity. Additionally, PRRs can detect perturbation of cellular homeostasis caused by pathogens and fine-tune the immune responses. Among PRRs, nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) have attracted particular interest in the context of cellular stress-induced inflammation during infection. Recently, mechanistic insights into the monitoring of cellular homeostasis perturbation by NLRs have been provided. We summarize the current knowledge about the disruption of cellular homeostasis by pathogens and focus on NLRs as innate immune sensors for its detection. We highlight the mechanisms employed by various pathogens to elicit cytoskeleton disruption, organelle stress as well as protein translation block, point out exemplary NLRs that guard cellular homeostasis during infection and introduce the concept of stress-associated molecular patterns (SAMPs). We postulate that integration of information about microbial patterns, danger signals, and SAMPs enables the innate immune system with adequate plasticity and precision in elaborating responses to microbes of variable virulence.

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Human Type I Interferon Antiviral Effects in Respiratory and Reemerging Viral Infections

Journal of Immunology Research ◽

10.1155/2020/1372494 ◽

2020 ◽

Vol 2020 ◽

pp. 1-27 ◽

Cited By ~ 4

Author(s):

Patricio L. Acosta ◽

Alana B. Byrne ◽

Diego R. Hijano ◽

Laura B. Talarico

Keyword(s):

Immune System ◽

Host Defense ◽

Immune Modulation ◽

Molecular Mechanisms ◽

Viral Infections ◽

Current Knowledge ◽

Type I Interferons ◽

Type I ◽

Antiviral Effects ◽

Wide Range

Type I interferons (IFN-I) are a group of related proteins that help regulate the activity of the immune system and play a key role in host defense against viral infections. Upon infection, the IFN-I are rapidly secreted and induce a wide range of effects that not only act upon innate immune cells but also modulate the adaptive immune system. While IFN-I and many IFN stimulated genes are well-known for their protective antiviral role, recent studies have associated them with potential pathogenic functions. In this review, we summarize the current knowledge regarding the complex effects of human IFN-I responses in respiratory as well as reemerging flavivirus infections of public health significance and the molecular mechanisms by which viral proteins antagonize the establishment of an antiviral host defense. Antiviral effects and immune modulation of IFN-stimulated genes is discussed in resisting and controlling pathogens. Understanding the mechanisms of these processes will be crucial in determining how viral replication can be effectively controlled and in developing safe and effective vaccines and novel therapeutic strategies.

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The role of the immune system in idiopathic nephrotic syndrome

Molecular and Cellular Pediatrics ◽

10.1186/s40348-021-00128-6 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Agnes Hackl ◽

Seif El Din Abo Zed ◽

Paul Diefenhardt ◽

Julia Binz-Lotter ◽

Rasmus Ehren ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Immune System ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Idiopathic Nephrotic Syndrome ◽

Cell Subset ◽

Causative Factor ◽

Direct Role ◽

Filtration Barrier

AbstractIdiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia and usually responds well to steroids. However, relapses are frequent, which can require multi-drug therapy with deleterious long-term side effects. In the last decades, different hypotheses on molecular mechanisms underlying INS have been proposed and several lines of evidences strongly indicate a crucial role of the immune system in the pathogenesis of non-genetic INS. INS is traditionally considered a T-cell-mediated disorder triggered by a circulating factor, which causes the impairment of the glomerular filtration barrier and subsequent proteinuria. Additionally, the imbalance between Th17/Tregs as well as Th2/Th1 has been implicated in the pathomechanism of INS. Interestingly, B-cells have gained attention, since rituximab, an anti-CD20 antibody demonstrated a good therapeutic response in the treatment of INS. Finally, recent findings indicate that even podocytes can act as antigen-presenting cells under inflammatory stimuli and play a direct role in activating cellular pathways that cause proteinuria. Even though our knowledge on the underlying mechanisms of INS is still incomplete, it became clear that instead of a traditionally implicated cell subset or one particular molecule as a causative factor for INS, a multi-step control system including soluble factors, immune cells, and podocytes is necessary to prevent the occurrence of INS. This present review aims to provide an overview of the current knowledge on this topic, since advances in our understanding of the immunopathogenesis of INS may help drive new tailored therapeutic approaches forward.

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A short overview of vitamin C and selected cells of the immune system

Open Medicine ◽

10.2478/s11536-010-0066-x ◽

2011 ◽

Vol 6 (1) ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Voja Pavlovic ◽

M. Sarac

Keyword(s):

Immune System ◽

Vitamin C ◽

Defense Mechanisms ◽

Molecular Mechanisms ◽

The Body ◽

Water Soluble ◽

Toxicological Effects ◽

Positive Effects ◽

Wide Range ◽

Vitamin C Supplementation

AbstractVitamin C (ascorbic acid) is an essential water-soluble nutrient that primarily exerts its effect on a host defense mechanisms and immune homeostasis and is the most important physiological antioxidant. Stable intake of vitamin C is essential for life in humans because the body does not synthesize it. Even the numerous studies have demonstrated that vitamin C supplementation stimulates the immune system, prevents DNA damage and significantly decreases the risk of a wide range of pathologies; the potential protective mechanisms are still largely unknown. This review summarizes the recently known facts about the role of vitamin C on the selected cells of the immune system and potential molecular mechanisms involved. Further, in this review, many new data about the positive effects of vitamin C on the immune system, potential toxicological effects, vitamin C supplementation in disease development, as well as some proposed mechanisms of vitamin C activity, are discussed.

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Role of Zinc in Immune System and Anti-Cancer Defense Mechanisms

Nutrients ◽

10.3390/nu11102273 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2273 ◽

Cited By ~ 24

Author(s):

Dorota Skrajnowska ◽

Barbara Bobrowska-Korczak

Keyword(s):

Immune System ◽

Defense Mechanisms ◽

Current Knowledge ◽

Cell Structure ◽

Antioxidant Properties ◽

Zinc Content ◽

Epidemiological Studies ◽

Enzyme Activation ◽

Anti Cancer ◽

Risk Of Cancer

The human body cannot store zinc reserves, so a deficiency can arise relatively quickly, e.g., through an improper diet. Severe zinc deficiency is rare, but mild deficiencies are common around the world. Many epidemiological studies have shown a relationship between the zinc content in the diet and the risk of cancer. The anti-cancer effect of zinc is most often associated with its antioxidant properties. However, this is just one of many possibilities, including the influence of zinc on the immune system, transcription factors, cell differentiation and proliferation, DNA and RNA synthesis and repair, enzyme activation or inhibition, the regulation of cellular signaling, and the stabilization of the cell structure and membranes. This study presents selected issues regarding the current knowledge of anti-cancer mechanisms involving this element.

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Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover

Viruses ◽

10.3390/v11020192 ◽

2019 ◽

Vol 11 (2) ◽

pp. 192 ◽

Cited By ~ 17

Author(s):

Sonu Subudhi ◽

Noreen Rapin ◽

Vikram Misra

Keyword(s):

Viral Load ◽

Immune System ◽

Virus Replication ◽

Defense Mechanisms ◽

Molecular Mechanisms ◽

Viral Persistence ◽

Latently Infected ◽

Unique Nature ◽

Immune System Modulation ◽

Perfect Storm

Bats harbor a myriad of viruses and some of these viruses may have spilled over to other species including humans. Spillover events are rare and several factors must align to create the “perfect storm” that would ultimately lead to a spillover. One of these factors is the increased shedding of virus by bats. Several studies have indicated that bats have unique defense mechanisms that allow them to be persistently or latently infected with viruses. Factors leading to an increase in the viral load of persistently infected bats would facilitate shedding of virus. This article reviews the unique nature of bat immune defenses that regulate virus replication and the various molecular mechanisms that play a role in altering the balanced bat–virus relationship.

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Dysfunctions, Molecular Mechanisms, and Therapeutic Strategies of Regulatory T Cells in Rheumatoid Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.716081 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaoya Li ◽

Huihui Xu ◽

Jing Huang ◽

Dan Luo ◽

Shuang Lv ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Immune System ◽

Regulatory T Cells ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Therapeutic Strategies ◽

Distinct Subpopulation ◽

Substantial Progress ◽

Fundamental Research

Regulatory T cells (Tregs) represent a distinct subpopulation of CD4+ T lymphocytes that promote immune tolerance and maintain immune system homeostasis. The dysfunction of Tregs is tightly associated with rheumatoid arthritis (RA). Although the complex pathogenic processes of RA remain unclear, studies on Tregs in RA have achieved substantial progress not only in fundamental research but also in clinical application. This review discusses the current knowledge of the characterizations, functions, and molecular mechanisms of Tregs in the pathogenesis of RA, and potential therapies for these disorders are also involved.

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Molecular Mechanisms of Borrelia burgdorferi Phagocytosis and Intracellular Processing by Human Macrophages

Biology ◽

10.3390/biology10070567 ◽

2021 ◽

Vol 10 (7) ◽

pp. 567

Author(s):

Philipp Woitzik ◽

Stefan Linder

Keyword(s):

Immune System ◽

Lyme Disease ◽

Borrelia Burgdorferi ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Human Macrophages ◽

Sequence Of Events ◽

Intracellular Processing ◽

Open Questions ◽

Causative Agents

Lyme disease is the most common vector-borne illness in North America and Europe. Its causative agents are spirochetes of the Borrelia burgdorferi sensu latu complex. Infection with borreliae can manifest in different tissues, most commonly in the skin and joints, but in severe cases also in the nervous systems and the heart. The immune response of the host is a crucial factor for preventing the development or progression of Lyme disease. Macrophages are part of the innate immune system and thus one of the first cells to encounter infecting borreliae. As professional phagocytes, they are capable of recognition, uptake, intracellular processing and final elimination of borreliae. This sequence of events involves the initial capture and internalization by actin-rich cellular protrusions, filopodia and coiling pseudopods. Uptake into phagosomes is followed by compaction of the elongated spirochetes and degradation in mature phagolysosomes. In this review, we discuss the current knowledge about the processes and molecular mechanisms involved in recognition, capturing, uptake and intracellular processing of Borrelia by human macrophages. Moreover, we highlight interactions between macrophages and other cells of the immune system during these processes and point out open questions in the intracellular processing of borreliae, which include potential escape strategies of Borrelia.

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Mesophyll conductance: the leaf corridors for photosynthesis

Biochemical Society Transactions ◽

10.1042/bst20190312 ◽

2020 ◽

Vol 48 (2) ◽

pp. 429-439 ◽

Cited By ~ 3

Author(s):

Jorge Gago ◽

Danilo M. Daloso ◽

Marc Carriquí ◽

Miquel Nadal ◽

Melanie Morales ◽

...

Keyword(s):

Molecular Mechanisms ◽

Current Knowledge ◽

Main Role ◽

Mesophyll Conductance ◽

Future Studies ◽

Cell Structures ◽

Leaf Tissues ◽

Change Framework ◽

Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

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The Immune System Regulation in Sepsis: From Innate to Adaptive

Current Protein and Peptide Science ◽

10.2174/1389203720666190305164128 ◽

2019 ◽

Vol 20 (8) ◽

pp. 799-816 ◽

Cited By ~ 6

Author(s):

Yue Qiu ◽

Guo-wei Tu ◽

Min-jie Ju ◽

Cheng Yang ◽

Zhe Luo

Keyword(s):

Clinical Trials ◽

Immune System ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Immune Cells ◽

Current Knowledge ◽

Systemic Inflammatory Response ◽

Immune System Regulation

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

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