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Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that affects mainly young people. It is believed that the autoimmune process observed in the pathogenesis of MS is influenced by a complex interaction between genetic and environmental factors, including infectious agents. The results of this study suggest the protective role of Toxoplasma gondii infections in MS. Interestingly, high Toxoplasma IgM seropositivity in MS patients receiving immunomodulatory drugs (IMDs) was identified. On the other hand, Borrelia infections seem to be positively associated with MS. Although the interpretation of our results is limited by the retrospective nature of the studies, the results strongly indicate that further experimental and clinical studies are needed to explain the role of infectious agents in the development and pathophysiological mechanisms of MS. [ABSTRACT FROM AUTHOR]

Parasitic nematodes and their products are promising candidates for therapeutics against inflammatory bowel diseases (IBD). Two species of nematodes, the hookworm Necator americanus and the whipworm Trichuis suis, are being used in clinical treatment trials of IBD referred to as "helminth therapy". Heligmosomoides polygyrus is a well-known model for human hookworm infections. Excretory–secretory (ES) products of H. polygyrus L4 stage that developed during colitis show a different immunomodulatory effect compared to the ES of H. polgyrus from healthy mice. The aim of the study was to evaluate excretory–secretory proteins produced by H. polygyrus L4 stage males and females that developed in the colitic milieu. Mass spectrometry was used to identify proteins. Blast2GO was used to investigate the functions of the discovered proteins. A total of 387 proteins were identified in the ES of H. polygyrus L4 males (HpC males), and 330 proteins were identified in the ES of L4 females that developed in the colitic milieu (HpC females). In contrast, only 200 proteins were identified in the ES of L4 males (Hp males) and 218 in the ES of L4 females (Hp females) that developed in control conditions. Most of the proteins (123) were detected in all groups. Unique proteins identified in the ES of HpC females included annexin, lysozyme-2, apyrase, and galectin. Venom allergen/Ancylostoma-secreted protein-like, transthyretin-like family proteins, and galectins were found in the secretome of HpC males but not in the secretome of control males. These molecules may be responsible for the therapeutic effects of nematodes in DSS-induced colitis. [ABSTRACT FROM AUTHOR]

Culturomics employs various cultivating conditions to obtain different types of bacteria and new species. However, current culturomics lacks a highly efficient method for isolating specific pathobionts. Immunomagnetic bead technology, which uses magnetic beads conjugated with antibodies for capturing the antigen to realize enrichment of the targets, has been employed as an alternative method. In this study, we developed a novel method, immunomagnetic bead‐enriched culturomics (IMBEC), in which magnetic bead‐conjugated antibodies purified from the fecal samples of patients with colorectal cancer (CRC) were used to enrich and isolate potential pathobionts. A protocol for enriching potential pathobionts via immunomagnetic capture was developed by optimizing the concentrations of coupling reagents, NaCl, and detergent. The efficacy of pathobiont enrichment was compared between antibody‐coated magnetic beads (antibody group) and nonconjugated blank magnetic beads (blank group). To determine the proinflammatory potential of isolates from both groups, we investigated their ability to induce cytokine production in THP‐1 macrophages. This protocol was employed for isolating bacteria from 10 fecal samples of patients with CRC, which were simultaneously compared with those isolated from the blank group. A total of 209 bacterial species were isolated from both groups, including 173 from the antibody group, 160 from the blank group, and 124 from both groups. Bacteria isolated from the antibody group produced more proinflammatory cytokines than those isolated from the blank group. IMBEC is a promising method for relatively specific isolation of potential pathobionts for a particular disease of interest. Highlights: We have developed a novel method called immunomagnetic bead‐enriched culturomics (IMBEC) to enrich and isolate colorectal cancer‐related pathobionts. This method combines immunomagnetic beads and culturomics technology.IMBEC can be targeted to isolate more bacterial species associated with cancer or inflammation, and can be accurate to the strain level.Bacterial DNA is not only detected in the blood of colorectal cancer patients but also in the serum of patients with other diseases, so IMBEC can also be employed in other diseases to isolate pathobionts. [ABSTRACT FROM AUTHOR]

I Diagnostics i was able to uphold its high standards for published papers due to the outstanding efforts of our reviewers. Regardless of whether the articles they examined were ultimately published, the editors would like to express their appreciation and thank the following reviewers for the time and dedication that they have shown I Diagnostics i : hose of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). Thanks to the efforts of our reviewers in 2022, the median time to first decision was 18 days and the median time to publication was 38 days. [Extracted from the article]

Nematode infection is a major threat to the health of humans, domestic animals and wildlife. Nematodes vary in their effect on the host and in the mechanisms underlying immunity but the general features are becoming clear. There is considerable variation among individuals in resistance to infection and much of this variation is due to genetic variation in the immune response. The major histocompatibility complex has a strong influence on resistance to infection but other genes are collectively more important. Resistant individuals produce more IgA, eosinophils, IgE and mast cells than susceptible individuals and this is a consequence of stronger type 2 (Th2) immune responses. A variety of factors promote Th2 responses including genetic background, diet, molecules produced by the parasite and the location of the infection. A variety of cells and molecules including proteins, glycolipids and RNA act in concert to promote responses and to regulate the response. Nematodes themselves also modulate the host response and over 20 parasite-derived immunomodulatory molecules have been identified. Different species of nematodes modulate the immune response in different ways and probably use multiple molecules. The reasons for this are unclear and the interactions among immunomodulators have still to be investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Helminths are parasitic worms that influence their host in a variety of ways, including the production of growth factors and the creation of blood vessels (angiogenesis). Parasites are used to control autoimmune diseases and parasite-derived molecules are widely studied for their therapeutic potential. Accordingly, the objective of this study was to evaluate the influence of parasitic nematode infection on growth factors related to angiogenesis in murine colitis and multiple sclerosis. We observed significant changes in both models of autoimmune disorders. In addition, parasitic infection remodeled the creation of vessels in the brains of mice with multiple sclerosis. Nematode-derived factors are promising tools to fight autoimmune diseases and to study angiogenesis. Accumulating data suggest an important role of growth factors in autoimmune diseases and parasitic nematode infections. Nematodes are used in clinical studies of autoimmune diseases and parasite-derived molecules are widely studied for their therapeutic potential in various types of disorders. However, the effect of nematode infection on growth factors in autoimmune disorders has not been studied. The objective of this study was to evaluate the influence of infection with the intestinal nematode Heligmosomoides polygyrus in murine autoimmune models on the production of growth factors. Here, the level of a variety of growth factors related mainly to angiogenesis was evaluated by protein array in the intestinal mucosa of C57BL/6 dextran sodium sulfate-induced colitic mice and in cerebral spinal fluid of experimental autoimmune encephalomyelitis (EAE) mice infected with nematodes. In addition, vessel formation was evaluated in the brains of EAE mice infected with H. polygyrus. A significant influence of nematode infection on the level of angiogenic factors was observed. Parasitic infection of colitic mice resulted in upregulation of mucosal AREG, EGF, FGF-2, and IGFBP-3 in the intestine of the host and better adaptation (infectivity). In EAE mice, infection increased the level of FGF-2 and FGF-7 in CSF. In addition, remodeling of brain vessels was observed, with a higher density of long vessels. Nematode-derived factors are promising tools to fight autoimmune diseases and to study angiogenesis. [ABSTRACT FROM AUTHOR]

Historically, there has been little interaction between parasitologists and oncologists, although some helminth infections predispose to the development of tumours. In addition, both parasites and tumours need to survive immune attack. Recent research suggests that both tumours and parasites suppress the immune response to increase their chances of survival. They both co-opt the transforming growth factor beta (TGFβ) signalling pathway to modulate the immune response to their benefit. In particular, there is concern that suppression of the immune response by nematodes and their products could enhance susceptibility to tumours in both natural and artificial infections. [ABSTRACT FROM AUTHOR]

Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing–remitting MS (RRMS) patients at an early phase of the disease. We examined the influence of demographic parameters on the distribution of CD4+ and CD8+ T cell subclasses by generalized linear modeling. We also studied the expression of the following markers—CTLA-4, GITR, PD-1, FoxP3, Helios, CD28, CD62L, CD103—on T cell subsets from peripheral blood with a 14-color flow cytometry panel. We used an antibody array to define the profiles of 34 Th1/Th2/Th17 cytokines in the serum. Expression of PD-1 and GITR on CD4+ and CD8+ Tregs was decreased in RRMS patients. The proinflammatory factors IFN-γ, IL-17, IL-17F, TGFβ-1, TGFβ-3, IL-1SRII, IL-12 p40, sgp130, IL-6sR were significantly increased in RRMS patients. Therefore, a deficiency of PD-1 and GITR immune checkpoints on CD4+ and CD8+ Tregs is a feature of RRMS and might underlie impaired T cell control. [ABSTRACT FROM AUTHOR]

Galectins are a family of proteins that bind β-galactosides and play key roles in a variety of cellular processes including host defence. They have been well studied in hosts but less so in gastrointestinal nematodes. Both host and parasite galectins are present in the gastrointestinal tract following infection. Parasite galectins can both bind antibody, especially highly glycosylated IgE and be bound by antibody. Parasite galectins may act as molecular sponges that soak up antibody. Host galectins promote mast cell degranulation while parasite galectins inhibit degranulation. Host and parasite galectins can also bind mucins and influence mucus viscosity. As the protective response against gastrointestinal nematode infection is partly dependent on IgE mediated mast cell degranulation and mucus, the interactions between host and parasite galectins play key roles in determining the outcome of infection. [ABSTRACT FROM AUTHOR]

Background: Excretory-secretory (ES) products are crucial in maintaining helminths in the host. Consequently, the proteins of ES are potential vaccine molecules and potential therapeutic agents for autoimmune diseases. Heligmosomoides polygyrus bakeri, a gastrointestinal parasite of mice, is a model of hookworm infection in humans. ES produced by both sexes of H. polygyrus bakeri L4 stage cultured separately shows different immunomodulatory properties than ES obtained when both sexes are cultured together. Accordingly, the objective of this study was to identify and compare the excretory-secretory molecules from single-sex and mixed cultures. Methods: The composition of ES of male and female L4 stage nematodes in the presence (cultured together) or absence (cultured alone) of the opposite sex was examined. Proteins were identified using mass spectrometry. The functions of identified proteins were explored with Blast2GO. Results: A total of 258 proteins derived from mixed larval culture in the presence of sex pheromones were identified, 160 proteins from pure female cultures and 172 from pure male cultures. Exposure of nematodes to the sex pheromones results in abundant production of proteins with immunomodulatory properties such as Val proteins, acetylcholinesterases, TGF-β mimic 9 and HpARI. Proteins found only in ES from mixed larval cultures were TGF-β mimics 6 and 7 as well as galectin. Conclusions: The presence of the opposite sex strongly influences the composition of ES products, probably by chemical (pheromone) communication between individuals. However, examination of the composition of ES from various conditions gives an opportunity for searching for new potentially therapeutic compounds and anthelminthics as well as components of vaccines. Manipulation of the nematode environment might be important for the studies on the immunomodulatory potential of nematodes. [ABSTRACT FROM AUTHOR]

Following organ transplantation, it is essential that immune tolerance is induced in the graft recipient to reduce the risk of rejection and avoid complications associated with the long-term use of immunosuppressive drugs. Immature dendritic cells (DCs) are considered to promote transplant tolerance and may minimize the risk of graft rejection. The aim of the study was to evaluate the effects of immunosuppressive agents: rapamycin (Rapa) and cyclosporine A (CsA) on generation of human tolerogenic DCs (tolDCs) and also to evaluate the ability of these cells to induce mechanisms of immune tolerance. tolDCs were generated in the environment of Rapa or CsA. Next, we evaluated the effects of these agents on surface phenotypes (CD11c, MHC II, CD40, CD80, CD83, CD86, CCR7, TLR2, TLR4), cytokine production (IL-4, IL-6, IL-10, IL-12p70, TGF-β), phagocytic capacity and resistant to lipopolysaccharide activation of these DCs. Moreover, we assessed ability of such tolDCs to induce T cell activation and apoptosis, Treg differentiation and production of Th1- and Th2-characteristic cytokine profile. Data obtained in this study demonstrate that rapamycin is effective at generating maturation-resistant tolDCs, however, does not change the ability of these cells to induce mechanisms of immune tolerance. In contrast, CsA affects the ability of these cells to induce mechanisms of immune tolerance, but is not efficient at generating maturation-resistant tolDCs. [ABSTRACT FROM AUTHOR]

The gastrointestinal nematode Heligmosomoides polygyrus bakeri shows enhanced survival in mice with colitis. As the antibody response plays an important role in antiparasitic immunity, antibodies against male and female L4 H. polygyrus were examined in mice with and without colitis. Levels of specific antibodies in the mucosa and serum were determined by enzyme-linked immunosorbent assay and immunogenic proteins of male and female parasites were identified using 2D electrophoresis and mass spectrometry. The function of identified proteins was explored with Blast2Go. Nematodes in mice with colitis induced higher levels of specific immunoglobulin G (IgG1) and IgA, a lower level of IgE in the small intestine and a higher level of IgE in serum against female L4. Infected mice with colitis recognized 12 proteins in male L4 and 10 in female L4. Most of the recognized proteins from male L4 were intermediate filament proteins, whereas the proteins from female L4 were primarily actins and galectins. Nematodes from mice with colitis were immunogenically different from nematodes from control mice. This phenomenon gives new insights into helminth therapy as well as host–parasite interactions. [ABSTRACT FROM AUTHOR]

Myeloid‐derived suppressor cells (MDSCs) are heterogeneous population of monocyte and granulocyte progenitors that are highly suppressive against T cells. In BALB/c mice infected with a nematode Heligmosomoides polygyrus bakeri, we studied the dynamics of MDSCs, identified as CD11b+Gr‐1+, induction in different tissues along with the development of parasite infection. We observed that MDSC‐like cells are induced both by larvae and adult stages of H polygyrus bakeri. Gr‐1+ cells of suppressive phenotype are recruited in the bone marrow, peripheral blood and peritoneal cavity during histotropic phase of infection and are present at that time in the intestine wall, where worms reside. Later, during intestinal phase, suppressive Gr‐1+ cells increased in mesenteric lymph nodes and the spleen. l‐arginine metabolism was important for the protective immunity, and parasite‐induced Gr‐1+ cells showed elevated arginase‐1 and iNOS expression. Inhibition of arginase‐1 and l‐arginine administration caused reduced level of infection that coincided with weaker suppressive phenotype of Gr‐1+ cells. We identified that l‐arginine pathway activation and induction of MDSC‐like cells characterize immunosuppressive state during H polygyrus bakeri infection in mice. Our findings confirm the role of MDSCs in parasitic infections and point l‐arginine pathway as a potential target for immunomodulation during nematode infections. [ABSTRACT FROM AUTHOR]

One of the most important scientific discoveries of recent years was the disclosure that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Scientists suggest that human gut microflora may even act as the "second brain" and be responsible for neurodegenerative disorders like Alzheimer's disease (AD). Although human-associated microbial communities are generally stable, they can be altered by common human actions and experiences. Enteric bacteria, commensal, and pathogenic microorganisms, may have a major impact on immune system, brain development, and behavior, as they are able to produce several neurotransmitters and neuromodulators like serotonin, kynurenine, catecholamine, etc., as well as amyloids. However, brain destructive mechanisms, that can lead to dementia and AD, start with the intestinal microbiome dysbiosis, development of local and systemic inflammation, and dysregulation of the gut-brain axis. Increased permeability of the gut epithelial barrier results in invasion of different bacteria, viruses, and their neuroactive products that support neuroinflammatory reactions in the brain. It seems that, inflammatory-infectious hypothesis of AD, with the great role of the gut microbiome, starts to gently push into the shadow the amyloid cascade hypothesis that has dominated for decades. It is strongly postulated that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. This is promising area for therapeutic intervention. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention, alter microbial partners and their products including amyloid protein, will probably become a new treatment for AD. [ABSTRACT FROM AUTHOR]

Copyright of Advances in Hygiene & Experimental Medicine / Postepy Higieny i Medycyny Doswiadczalnej is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Helminths use various immunomodulatory and anti-inflammatory strategies to evade immune attack by the host. During pathological conditions, these strategies alter the course of disease by reducing immune-mediated pathology. The study examines the therapeutic effect of the nematode L4 stage based on an in vivo model of multiple sclerosis, monophasic encephalomyelitis (EAE), induced by sensitization with MOG35-55 peptide in C57BL/6 female mice infected with the intestinal nematode Heligmosomoides polygyrus. The EAE remission was correlated with altered leukocyte number identified in the central nervous system (CNS), and temporary permeability of the blood-brain barrier at the histotrophic phase of infection. At 6 days post-infection, when the L4 stage had almost completely attenuated the clinical severity and pathological signs of EAE, CD25+ cell numbers expanded significantly, with parallel growth of CD8+ and CD4+, both CD25+Foxp3+ and CD25+Foxp3− subsets and alternatively activated macrophages. The phenotypic changes in distinct subsets of cerebrospinal fluid cells were correlated with an inhibited proliferative response of encephalitogenic T cells and elevated levels of nerve growth factor and TGF-β. These results enhance our understanding of mechanisms involved in the inhibition of immune responses in the CNS during nematode infection. [ABSTRACT FROM AUTHOR]

Copyright of Edukacja Biologiczna i Środowiskowa is the property of Educational Research Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The purpose of this study was to evaluate the potential of chitosan units released during natural degradation of the polymer to activate the immune system against T. spiralis infection. High molecular weight chitosan was injected intraperitoneally into C57BL/6 mice. Flow cytometry and cytokine concentration, measured by ELISA, were used to characterize peritoneal cell populations during T. spiralis infection. The strong chemo-attractive properties of chitosan caused considerable infiltration into the peritoneal cavity of CD11b+ cells, with reduced expression of MHC class II, CD80, CD86, Dectin-1 or CD23 receptors in comparison to T. spiralis-infected mice. After prolonged chitosan biodegradation, cell populations expressing IL-4R, MR and Dectin-1 receptors were found to coexist with elevated IL-6, IL-10, TGF-β and IgA production. IgA cross-reacted with T. spiralis antigen and chitosan. It was found that chitosan treatment attracted immune cells with low activity, which resulted in the number of nematodes increasing. The glucosamine and N-acetyl-D-glucosamine residues were recognized by wheat germ agglutinin (WGA) lectin and therefore any biodegradable chitosan units may actively downregulate the immune response to the parasite. The findings are relevant for both people and animals treated with chitosan preparations. [ABSTRACT FROM AUTHOR]

The probability of infection with fungi, as well as parasitic nematodes or arthropods may increase in overcrowded population of animals and human. The widespread overuse of drugs and immunosuppressants for veterinary or medical treatment create an opportunity for many pathogenic species. The aim of the review is to present the common molecular characteristics of such pathogens as fungi and nematodes and other chitin bearing animals, which may both activate and downregulate the immune response of the host. Although these pathogens are evolutionary distinct and distant, they may provoke similar immune mechanisms. The role of chitin in these phenomena will be reviewed, highlighting the immune reactions that may be induced in mammals by this natural polymer. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are increasingly recognized as disease entities in which dysregulated cytokines contribute to tissue-specific inflammation. In organ-specific and multiorgan autoimmune diseases, the cytokine profiles show some similarities. Despite these similarities, the cytokines have different roles in the pathogenesis of different diseases. Altered levels or action of cytokines can result from changes in cell signaling. This article describes alterations in the JAK-STAT, TGF-β and NF-κB signaling pathways, which are involved in the pathogenesis of multiple sclerosis and systemic lupus erythematosus. There is a special focus on T cells in preclinical models and in patients afflicted with these chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Summary: Nematode infection is one of the principal diseases suffered by sheep and the class II region of the MHC has been repeatedly associated with differences in susceptibility and resistance to infection. The aim of this study was to examine the association of MHC class II haplotypes in a flock of Texel sheep with faecal egg counts and antibody responsiveness. Two haplotypes carried the DRB1*11:01 allele which has previously been associated with reduced egg counts in Scottish Blackface and Suffolk sheep. One of the two haplotypes was associated with reduced egg counts in the Texel breed, and both haplotypes were associated with reduced IgA activity against an extract from fourth‐stage larvae. The reduced IgA activity is probably a consequence of reduced numbers of fourth‐stage larvae in sheep carrying the resistance allele. The association of specific MHC alleles with reduced egg counts, reduced worm numbers and decreased IgA activity provides a mechanism for the density‐dependent regulation of parasite growth and fecundity. [ABSTRACT FROM AUTHOR]