Beata Tokarz-Deptuła

Proposal for a unified classification system and nomenclature of lagoviruses

Lagoviruses belong to the Caliciviridae family. They were first recognized as highly pathogenic viruses of the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus) that emerged in the 1970-1980s, namely, rabbit haemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV), according to the host species from which they had been first detected. However, the diversity of lagoviruses has recently expanded to include new related viruses with varying pathogenicity, geographic distribution and host ranges. Together with the frequent recombination observed amongst circulating viruses, there is a clear need to establish precise guidelines for classifying and naming lagovirus strains. Therefore, here we propose a new nomenclature based on phylogenetic relationships. In this new nomenclature, a single species of lagovirus would be recognized and called Lagovirus europaeus. The species would be divided into two genogroups that correspond to RHDV- and EBHSV-related viruses, respectively. Genogroups could be subdivided into genotypes, which could themselves be subdivided into phylogenetically well-supported variants. Based on available sequences, pairwise distance cutoffs have been defined, but with the accumulation of new sequences these cutoffs may need to be revised. We propose that an international working group could coordinate the nomenclature of lagoviruses and any proposals for revision.

[NET and NETosis--new phenomenon in immunology].

Neutrophils are one of the first cells of the immune system recruited to the site of infection, representing the hosts most effective and numerous front-line defenders. Recently, a novel antimicrobial mechanism of neutrophils has been described: upon activation, they release DNA and a subset of their granule content, forming neutrophil extracellular traps (NETs). These extracellular, chromatin structures, which contain histones and neutrophil granule proteins, can trap and kill a broad spectrum of microbes, including Gram-positive and Gram-negative bacteria, fungi, protozoa and viruses. Some of the pathogens, which are trapped and exposed to high local concentrations of antimicrobial compounds, employ strategies against NET binding, including surface modification and/or degradation of NET by DNases. It has been suggested that NETs are formed during active cell death, recently named NETosis. New data indicate that this novel mechanism of cell death requires interaction between three processes--reactive oxygen species generation, histone citrullination and autophagy--and significantly differs from previously known types of cell death, including apoptosis and necrosis. Moreover, the release of nuclear chromatin was also described for other types of cells--mast cells and eosinophils. Mast cells, like neutrophils, under certain conditions release nuclear chromatin and may undergo a similar active cell death program, while eosinophils release only mitochondrial chromatin, and its release does not lead to the death of these cells.

Mechanisms of type I interferon action and its role in infections and diseases transmission in mammals

Interferons (IFNs) are pivotal regulators of immunological processes. This paper describes mainly type I interferons -α and -β and their recently recounted signaling pathways, especially connected with ISGs - interferon stimulated genes, having a crucial role in regulating IFN recruitment. Moreover, the paper shows the data on the role of interferons -α and -β in infections - not only commonly known viral infections, but also bacterial, fungal and parasitic.

Expression of IL-1β, IL-2, IL-10, TNF-β and GM-CSF in peripheral blood leukocytes of rabbits experimentally infected with rabbit haemorrhagic disease virus.

Rabbit haemorrhagic disease (RHD) is a highly morbid and mortal viral infection of European rabbits. This disease is one of the main causes of death in wild rabbits, and results in large economic losses in farms of rabbits worldwide. Although the first outbreak of this disease was noted in 1984, the pathogenesis of RHD and mechanisms of RHDV (rabbit haemorrhagic disease virus) pathogenecity have still not been fully elucidated. Recent studies indicate a role of the immune response, especially peripheral blood leukocytes (PBL), in the pathogenesis of this disease. Thus, in the present study we investigated the expression of IL-1β, IL-2, IL-10, TNF-β and GM-CSF genes in PBL of RHDV-infected rabbits. We also compared the expression of genes encoding these cytokines in rabbits with different course of RHDV infection (in animals that died 36h postinfection or survived until 60th h after infection). The study revealed that three (IL-10, TNF-β and GM-CSF) out of five investigated genes encoding cytokines showed increased expression in PBL of RHDV-infected rabbits, and the level of expression depended on the course of RHD. The results indicate the potential role of these cytokines in RHDV infection and their influence on the survival time of infected rabbits.

Stress granules (SG) and processing bodies (PB) in viral infections.

During reaction to stress caused by viral infection, RNA granules are formed in order to protect mRNA. Stress granules (SG) and processing bodies (PB) provide cell homeostasis and mRNA stability. They are formed, for example, during polio virus and MRV (mammalian orthoreovirus) infections. Some viruses, such as influenza virus and HTLV-1 (Human T-lymphotropic virus 1), block the formation of granules. In addition, there are viruses like West Nile Virus, Hepatitis C Virus (HCV) or human Herpes viruses, which influence the functioning of the granules.

Antifungal immunity in selected fungal infections.

Fungi are omnipresent in the environment; hence they are frequent factors causing infections in humans and animals even if their immune system works correctly. These facts stimulated interest in and the will to understand the antifungal immunity mechanisms. It has been, however, evidenced that the immunological response to mycotic pathogens is related to the species and morphological form of the fungus. Nevertheless, it is assumed that always in the antifungal response, there are mechanisms of innate and adaptive immunity that cooperate with one another to eliminate such pathogens. It has been evidenced that the main elements of antifungal immunity are physical barriers of the organism, phagocytosis, cytotoxicity, and possibly trogocytosis of PMN and MN cells, as well as T-cells, and to a smaller extent B-cells, the proportion of which is principally related to their products activating the processes of PMN and MN cells. An important role in this immunity also belongs to PRR, which activate the main processes of phagocytosis and cytotoxicity of PMN, MN, NK and DC cells.

Excitotoxicity and Wallerian degeneration as a processes related to cell death in nervous system.

Cell death is one of the processes that are currently extensively studied. Beside the commonly used terminology regarding cell death, i.e. apoptosis, autophagy, necrosis, and cornification, in recent years there has been a growing number of additional definitions of this process, such as mitotic catastrophe, anoikis, entosis, paraptosis, pyroptosis, pyronecrosis, excitotoxicity, and Wallerian degeneration, which are described in 2009 by the Nomenclature Committee on Cell Death as atypical. The recent report of that Committee significantly alter the classification and nomenclature of the cell death processes, in which excitotoxicity and Wallerian degeneration have not been taken into account. Thus the present review describes excitotoxicity, and Wallerian degeneration, as two processes associated to cell death phenomena characteristic for nervous system. Excitotoxicity is a neuronal death caused by excessive, or prolonged activation of receptors for the excitatory amino acids. Depending on the intensity of the initiating stimulus, the excitotoxicity may overlap with other types of cell death such as apoptosis and necrosis. Wallerian degeneration is a process that results when a nerve fiber is cut or crushed, in which the part of the axon separated from the neurons cell body degenerates distal to the injury. Wallerian degeneration is not a typical cell death mechanism, since neurons undergoing this process remain alive.

Coronins and their role in immunological phenomena

Coronins are a large family of proteins occurring in many eukaryotes. In mammals, seven coronin genes have been identified, evidencing that coronins 1 to 6 present classic coronin structure, while coronin 7 is a tandem coronin particle, without a spiral domain, although the best characterised coronin, in terms of both structure and function, is the mammalian coronin 1. It has been proven that they are related to regulation of actin dynamics, e.g. as a result of interaction with the complex of proteins Arp2/3. These proteins also modulate the activity of immune system cells, including lymphocyte T and B cells, neutrophils and macrophages. They are involved in bacterial infections with Mycobacterium tuberculosis, M. leprae and Helicobacter pylori and participate in the response to viral infections, e.g. infections of lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis Indiana virus (VSV). Also their involvement in autoimmune diseases such as lupus erythematosus has been recorded.

Characteristic of innate lymphoid cells (ILC)

Innate lymphoid cells (ILC) is a newly described family of immune cells that are part of the natural immunity which is important not only during infections caused by microorganisms, but also in the formation of lymphoid tissue, tissue remodeling after damage due to injury and homeostasis tissue stromal cells. Family ILC cells form NK cells (natural killer) and lymphoid tissue inducer T cells (LTi), which, although they have different functions, are evolutionarily related. NK cells are producing mainly IFN-γ, whereas LTi cells as NKR+LTi like, IL-17 and/or IL-22, which suggests that the last two cells, can also represent the innate versions of helper T cell--TH17 and TH22. Third population of ILC is formed by cells with characteristics such as NK cells and LTi (ILC22)--which are named NK22 cells, natural cytotoxicity receptor 22 (NCR22) cells or NK receptor-positive (LTi NKR+) LTi cells. Fourth population of ILC cells are ILC17--producing IL-17, while the fifth is formed by natural helper type 2 T cells (nTH2), nuocyte, innate type 2 helper cells (IH2) and multi-potent progenitor type 2 cells (MPPtype2). Cells of the last population synthesize IL-5 and IL-13. It is assumed that an extraordinary functional diversity of ILC family, resembles T cells, probably because they are under the control of the corresponding transcription factors - as direct regulation factors, such as the family of lymphocytes T.

Immunological memory cells

This article reviews immunological memory cells, currently represented by T and B lymphocytes and natural killer (NK) cells, which determine a rapid and effective response against a second encounter with the same antigen. Among T lymphocytes, functions of memory cells are provided by their subsets: central memory, effector memory, tissue-resident memory, regulatory memory and stem memory T cells. Memory T and B lymphocytes have an essential role in the immunity against microbial pathogens but are also involved in autoimmunity and maternal-fetal tolerance. Furthermore, the evidence of immunological memory has been established for NK cells. NK cells can respond to haptens or viruses, which results in generation of antigen-specific memory cells. T, B and NK cells, which have a role in immunological memory, have been characterized phenotypically and functionally. During the secondary immune response, these cells are involved in the reaction against foreign antigens, including pathogens, and take part in autoimmune diseases, but also are crucial to immunological tolerance and vaccine therapy.