Immune Response Research Articles

Alleviating effects of Gracilaria verrucosa supplement on non-specific immunity, antioxidant capacity and immune-related genes of pacific white shrimp (Litopenaeus vannamei) provoked with white spot syndrome virus

Our work evaluated the possible underlying roles of dietary dried seaweed (Gracilaria verrucosa; GV) on the inherent immune response, antioxidant capacity, immune-related gene expression, and protection of whiteleg shrimp (Litopenaeus vannamei) contra white spot syndrome virus (WSSV). Three hundred and sixty healthy L. vannamei (15.26 g ± 1.29 g) were graded into four supplemental groups ( Triplicate/group) and fed with diets including 0 (control), 2, 4, and 8 g GV (kg diet) −1 for 21 days. Following the feeding period, each group of shrimp received an intramuscular WSSV injection (1.4 × 106 copies/ml). Hemolymph and gills samples were collected before and after the challenge with WSSV. Notably, the administration of dietary GV significantly enhanced the innate immune parameters of pacific white shrimp including total hemocyte count (THC), phagocytosis, phenoloxidase activity, reactive oxygen species (ROS) production, and lysozyme activity before and after challenge with WSSV. Additionally, dietary supplementation of 4, and 8 g of GV (kg diet)−1 remarkably elevated ACP, AKP, SOD, GPx, and catalase activities along with a decrease in the MDA level in gills of shrimp before and post-WSSV challenge. In response to the GV supplement, significant upregulation of expression of ALF1, CRU1, PEN4, and CTL with downregulation of TRAF6, STAT, TLR1, and NOS genes was recorded in the gills tissue before and post-challenge with WSSV, especially at a dose of 8.0 GV g kg − 1. Dietary inoculated shrimp with GV revealed notably higher survival percentages after being challenged with WSSV. Conclusively, these data indicate that Gracilaria verrucosa can be recommended as a valuable supplemented seaweed to stimulate the innate immunity and enhance the health of Litopenaeus vannamei against viral infection.

Pangenome analysis of five representative Tropheryma whipplei strains following multiepitope-based vaccine design via immunoinformatic approaches.

Whipple disease caused by Tropheryma whipplei a gram-positive bacterium is a systemic disorder that impacts not only the gastrointestinal tract but also the vascular system, joints, central nervous system, and cardiovascular system. Due to the lack of an approved vaccine, this study aimed to utilize immunoinformatic approaches to design multiepitope -based vaccine by utilizing the proteomes of five representative T. whipplei strains. The genomes initially comprised a total of 4,844 proteins ranging from 956 to 1012 proteins per strain. We collected 829 nonredundant lists of core proteins, that were shared among all the strains. Following subtractive proteomics, one extracellular protein, WP_033800108.1, a WhiB family transcriptional regulator, was selected for the chimeric-based multiepitope vaccine. Five immunodominant epitopes were retrieved from the WhiB family transcriptional regulator protein, indicating MHC-I and MHC-II with a global population coverage of 70.61%. The strong binding affinity, high solubility, nontoxicity, nonallergenic properties and high antigenicity scores make the selected epitopes more appropriate. Integration of the epitopes into a chimeric vaccine was carried out by applying appropriate adjuvant molecules and linkers, leading to the vaccine construct having enhanced immunogenicity and successfully eliciting both innate and adaptive immune responses. Moreover, the abilityof the vaccine to bind TLR4, a core innate immune receptor, was confirmed. Molecular dynamics simulations have also revealed the promising potential stability of the designed vaccine at 400 ns. In summary, we have designed a potential vaccine construct that has the ability not only to induce targeted immunogenicity for one strain but also for global T. whipplei strains. This study proposes a potential universal vaccine, reducing Whipple's disease risk and laying the groundwork for future research on multi-strain pathogens.

The Variability of the Salivary Antimicrobial Peptide Profile: Impact of Lifestyle

Saliva is crucial in maintaining oral health; its composition reflects the body’s physiological and diseased state. Among salivary components, antimicrobial peptides (AMPs) stand out for their broad antimicrobial activities and role in modulating the oral microbiota and innate immune response. Local and systemic diseases can affect the levels of AMPs in saliva, making them attractive biomarkers. However, the large variability in their concentrations hampers their use in diagnostics. Knowledge of the various factors influencing the profile of salivary AMPs is essential for their use as biomarkers. Here, we examine how lifestyle factors such as physical activity, dietary supplementation, tobacco smoking, and psychological stress impact salivary AMP levels. By understanding these sources of variability, we can take a step forward in using AMPs for diagnostics and prognostics and develop new tailored and preventative approaches.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Dependent Attenuation of Tear Hyperosmolarity and Immune Cell-Driven Inflammation in the Eyes of Patients with Dry Eye Disease

Background: Dry eye disease (DED) is a chronic condition characterized by a decrease in tear production or an increase in tear evaporation, leading to inflammation and damage of the ocular surface. Dysfunction of ion channels, tear hyperosmolarity and immune cell-driven inflammation create a vicious circle responsible for the pathological changes in the eyes of DED patients. Mesenchymal stem cells (MSCs) are adult, rapidly proliferating stem cells that produce a large number of immunoregulatory, angiomodulatory, and growth factors that efficiently reduce tear hyperosmolarity-induced pathological changes, inhibit harmful immune response, and provide trophic support to the injured corneal and conjuctival epithelial cells, goblet cells and acinar cells in lacrimal glands of DED patients. Methods: An extensive research in the literature was implemented in order to elucidate the role of MSCs in the attenuation of tear hyperosmolarity and eye inflammation in patients suffering from DED. Results: Findings obtained in preclinical and pilot clinical studies demonstrated that MSCs reduced tear hyperomsolaity-induced pathological changes and suppressed immune cell-driven eye inflammation. Additionally, MSC-based therapy managed to successfully address the most severe DED-related conditions and complications. Conclusions: MSCs should be considered as potentially new therapeutic agents for the treatment of severe DED.

Cullin-Conciliated Regulation of Plant Immune Responses: Implications for Sustainable Crop Protection

Cullins are crucial components of the ubiquitin–proteasome system, playing pivotal roles in the regulation of protein metabolism. This review provides insight into the wide-ranging functions of cullins, particularly focusing on their impact on plant growth, development, and environmental stress responses. By modulating cullin-mediated protein mechanisms, researchers can fine-tune hormone-signaling networks to improve various agronomic traits, including plant architecture, flowering time, fruit development, and nutrient uptake. Furthermore, the targeted manipulation of cullins that are involved in hormone-signaling pathways, e.g., cytokinin, auxin, gibberellin, abscisic acids, and ethylene, can boost crop growth and development while increasing yield and enhancing stress tolerance. Furthermore, cullins also play important roles in plant defense mechanisms through regulating the defense-associated protein metabolism, thus boosting resistance to pathogens and pests. Additionally, this review highlights the potential of integrating cullin-based strategies with advanced biological tools, such as CRISPR/Cas9-mediated genome editing, genetic engineering, marker-associated selections, gene overexpression, and gene knockout, to achieve precise modifications for crop improvement and sustainable agriculture, with the promise of creating resilient, high-yielding, and environmentally friendly crop varieties.

Ro5-4864, a translocator protein ligand, regulates T cell-mediated inflammatory responses in skin.

Translocator protein (TSPO) is a mitochondrial outer membrane protein expressed on a variety of immune cells, including macrophages, dendritic cells, and T cells, in addition to neurons and steroid-producing cells. Previous studies of TSPO ligands have suggested that TSPO is involved in multiple cellular functions, including steroidogenesis, immunomodulation, and cell proliferation. Currently, there are limited reports on the effects of TSPO or TSPO ligands on T cell-mediated immune responses. We here investigated the involvement of TSPO/TSPO ligand in T cell responses using a 2,4-dinitro-1-fluorobenzene (DNFB)-induced contact hypersensitivity (CH) model. Treatment with Ro5-4864, a TSPO ligand, during DNFB sensitization reduced the number and activation status of CD4+ and CD8+ T cells in draining lymph nodes and alleviated skin inflammation after DNFB challenge. Adoptive transfer of Ro5-4864-treated mouse-derived DNFB-sensitized T cells to naïve mice inhibited CH responses after DNFB challenge. Ro5-4864-treated sensitized T cells showed lower proliferative responses when stimulated with DNFB-pulsed antigen-presenting cells compared to control-treated sensitized T cells. Ro5-4864 also suppressed cell proliferation, as well as adenosine triphosphate and lactate production, during T cell activation. Moreover, the inhibitory effects of Ro5-4864 on T cell responses were conserved in TSPO-deficient cells. Our results suggest that Ro5-4864 inhibits CH responses by suppressing energy metabolism, at least via glycolysis, to reduce the T cell primary response in a TSPO-independent manner.

Permeability-Controlled Probe for Ratiometric Detection of Plasma Membrane Integrity and Late Apoptosis.

The destruction of plasma membrane integrity is closely related to immune response, neuronal injury, cell apoptosis, and other pathological events. However, the construction of ratiometric fluorescent probes capable of detecting plasma membrane integrity remains a significant challenge, hindering in-depth studies on related biomedical areas. Herein, a polarity-responsive fluorescent probe was constructed for the ratiometric detection of cell membrane integrity for the first time. The probe targeted intact plasma membranes in healthy cells and relocated into the cytoplasm to give significantly red-shifted fluorescence after plasma membrane damage. Molecular simulations revealed that the high transmembrane barrier and amphipathic nature of the probe were responsible for its targeting ability. With the probe, the ratiometric detection of late apoptosis stage was realized for the first time, and the membrane damage of tumor cells induced by UV irradiation, toxins, and antitumor drugs was visualized. The effect of formaldehyde on membrane integrity was evaluated using a probe, and cysteine was proved to be a potential detoxifier to counteract the toxicity of formaldehyde.

Advances in the study of artemisinin and its derivatives for the treatment of rheumatic skeletal disorders, autoimmune inflammatory diseases, and autoimmune disorders: a comprehensive review

Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications.

An ionic liquid-based adjuvant for modulating cellular and humoral immune responses

Vaccination is an important strategy for the prevention of infectious diseases worldwide. Adjuvants can be incorporated in vaccine formulations to enhance the resultant immune response and subsequently confer more robust protection upon natural infection. While adjuvants have exciting potential to improve vaccination, the landscape of materials employed in clinical adjuvants is small and its expansion is needed to facilitate vaccine development against current and future infectious diseases. This study introduces the first ionic liquid (IL) adjuvant comprised of choline and sorbic acid (ChoSorb) to produce an antigen-specific cellular as well as humoral immune response against multiple antigens. The abilities of ChoSorb as a vaccine adjuvant is evaluated and characterized through material analysis, innate immune responses, and adaptive responses to both a model and clinical grade antigen. With the robust immune responses generated by ChoSorb and the accompanying mechanistic insights, this study introduces ILs as a new class of adjuvant materials for future vaccine design.

Recombinant leptins affect lipid metabolism in hepatocytes of Cynoglossus semilaevis

Leptin is a peptide hormone primarily produced by adipose tissue, which plays a crucial role in regulating energy balance by controlling appetite and energy expenditure. To better understand the intricate physiological functions of leptin in hepatocytes in tongue sole (Cynoglossus semilaevis), this study presents an integrated transcriptomic and metabolomic analysis of tongue sole hepatocytes following stimulation with lepA and lepB. Comparative analysis identified 2971 and 2900 upregulated differentially expressed genes (DEGs) and 1895 and 1821 downregulated DEGs in response to lepA and lepB stimulation, respectively. Notably, 5706 genes were commonly regulated by both stimulations, suggesting overlapping functional roles of these two leptin proteins. GO and KEGG enrichment analysis indicated significant enrichment in immune response (JAK-STAT signaling pathway, NF-κB signaling pathway, etc.) and lipid metabolism pathways, such as fatty acid synthesis, with similar findings for lepB. Metabolomic analysis demonstrated clear separation between treatment and control groups, with 34 medium- to long-chain fatty acids and numerous differentially expressed metabolites (DEMs) identified. KEGG analysis of the metabolome paralleled the transcriptomic findings, with shared pathways in lipid metabolism and immune function. Finally, joint analysis highlighted co-enrichment in linoleic acid metabolism and leishmaniasis pathways. Detailed mechanistic insights revealed the activation of JAK-STAT and NF-κB signaling pathways, modulation of arachidonic acid metabolism, and the influence on the MAPK signaling pathway. Additionally, lepA uniquely co-enriched in the fatty acid synthesis pathway, with specific gene regulation affecting the synthesis of various fatty acids. The study concluded that lepA and lepB exerted significant regulatory effects on lipid metabolism and immune responses in tongue sole hepatocytes through complex molecular networks. To our current knowledge, this represents the first direct evidence of leptin's role in immune function within teleost fish and offers valuable insights into the molecular mechanisms of lipid metabolism underlying the actions of lepA and lepB.

Antibodies to HIV-1 gp120 in an experimental model of atherosclerosis caused by immunization with native high-density lipoproteins

Antibodies to bacterial and viral antigens are detected in some systematic autoimmune diseases in the absence of infection. Autoimmune MRL mice and patients with mixed connective tissue disease produce antibodies to gp120 HIV-1, despite the fact that they had never been exposed to HIV-1. Conversely, viral infections may be accompanied by pathological autoimmune reactions. Reactivity to viral antigens in autoimmune diseases and autoimmune reactions in viral diseases are caused by the induction of antibodies via idiotype-anti-idiotype interactions between autoclones and lymphocyte clones against foreign antigens or homology of foreign antigens and autoantigens. Cardiovascular diseases caused by atherosclerosis are currently one of the main causes of mortality in HIV infected patients. It is assumed that HIV infection accelerates atherogenesis. The mechanisms of the association between HIV infection and atherosclerosis are not completely clear. Chronic activation of the immune system, disturbance of cytokine regulation caused by HIV infection, induction of autoantibodies against oxidized low-density lipoproteins (LDL) and antibodies to ApoB-D are considered as possible factors of atherogenesis in HIV infection. The aim of this research was to determine whether an atherogenic immune response against native human high-density lipoproteins (nHDL) could induce antibodies to gp120 HIV-1. Studies were conducted on model of autoimmune atherosclerosis caused by immunization with native human HDL in rabbits. Rabbits (n = 6) were one-time intradermally immunized with human nHDL at a dose of 200 μg of protein per animal in incomplete Freund’s adjuvant. Antibodies to gp120 HIV-1 were measured before immunization of rabbits and on the 28th and 42th day after immunization with HDL, and antibodies to HDL were weekly measured within 42 days after immunization. Histological analysis of the aorta was conducted after eight months after immunization. Transient anti-gp120 HIV-1 antibody production was detected in rabbits immunized with native HDL. The appearance of antibodies to gp120 HIV-1 in response to immunization with native HDL which causes atherosclerosis suggests that the immune response to gp120 HIV-1 during HIV infection may be accompanied by the production of atherogenic antibodies to HDL. Consequently, the antibodies to native lipoproteins caused by an immune response against gp120 HIV-1 may be a factor in atherogenesis during HIV-1 infection.

A TLR7 Agonist Conjugated to a Nanofibrous Peptide Hydrogel as a Potent Vaccine Adjuvant.

Toll-like receptors (TLRs) recognize pathogen- and damage-associated molecular patterns and, in turn, trigger the release of cytokines and other immunostimulatory molecules. As a result, TLR agonists are increasingly being investigated as vaccine adjuvants. Many of these agonists are small molecules that quickly diffuse away from the vaccination site, limiting their co-localization with antigens and, thus, their effect. Here, the small-molecule TLR7 agonist 1V209 is conjugated to a positively-charged multidomain peptide (MDP) hydrogel, K2, which was previously shown to act as an adjuvant promoting humoral immunity. Mixing the 1V209-conjugated K2 50:50 with the unfunctionalized K2 produces hydrogels that retain the shear-thinning and self-healing physical properties of the original MDP while improving the solubility of 1V209 more than 200-fold compared to the unconjugated molecule. When co-delivered with ovalbumin as a model antigen, 1V209-functionalized K2 produces a robust Th2 immune response and an antigen-specific Th1 immune response superior to alum, a widely used vaccine adjuvant. Together, these results suggest that K2 MDP hydrogels functionalized with 1V209 are a promising adjuvant for vaccines against infectious diseases, especially those benefiting from a combined Th1 and Th2 immune response.

Immunology of Stress: A Review Article

Stress significantly impacts the immune system, affecting susceptibility to illness and overall health. This review examines the intricate relationship between stress and the immune system, offering insights having practical implications for health and disease prevention. Stress can significantly trigger molecular and immune modulation, affecting the distribution and trafficking of immune cells in various organs and altering their composition in the blood. The review delves into two key pathways connecting stress and immunity: the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system. Stress activates the neuroendocrine system and triggers microglia in the brain, releasing stress hormones and neurotransmitters that modulate the function and movement of immune cells. Acute stress can temporarily strengthen immunity and promote protection during infection; in contrast, chronic stress dysregulates or inhibits immune functions. Chronic stress causes an increase in cortisol levels through the HPA axis, ultimately suppressing the immune response. Recognizing stress triggers and implementing effective stress management techniques can significantly impact individuals’ well-being. This review indicates that immune cells express genes differentially in response to stress, suggesting individual variabilities in the immune response against stress. This underscores the need for a personalized approach to stress management. This review also highlights the potential link between chronic stress and autoimmune disorders and warrants further investigation.

Impact of Sublethal Insecticides Exposure on Vespa magnifica: Insights from Physiological and Transcriptomic Analyses

Insecticides are widely used to boost crop yields, but their effects on non-target insects like Vespa magnifica are still poorly understood. Despite its ecological and economic significance, Vespa magnifica has been largely neglected in risk assessments. This study employed physiological, biochemical, and transcriptomic analyses to investigate the impact of sublethal concentrations of thiamethoxam, avermectin, chlorfenapyr, and β-cypermethrin on Vespa magnifica. Although larval survival rates remained unchanged, both pupation and fledge rates were significantly reduced. Enzymatic assays indicated an upregulation of superoxide dismutase and catalase activity alongside a suppression of peroxidase under insecticide stress. Transcriptomic analysis revealed increased adenosine triphosphate-related processes and mitochondrial electron transport activity, suggesting elevated energy expenditure to counter insecticide exposure, potentially impairing essential functions like flight, hunting, and immune response. The enrichment of pathways such as glycolysis, hypoxia-inducible factor signaling, and cholinergic synaptic metabolism under insecticide stress highlights the complexity of the molecular response with notable effects on learning, memory, and detoxification processes. These findings underscore the broader ecological risks of insecticide exposure to non-target insects and highlight the need for further research into the long-term effects of newer insecticides along with the development of strategies to safeguard beneficial insect populations.

Effect of RTS,S/AS01E vaccine booster dose on cellular immune responses in African infants and children

RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.

A multivalent RSV vaccine based on the modified vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a phase 3 clinical study

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV.Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period.In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified.MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).

Cytokine balance in pregnant women with preeclampsia

Studies were conducted to study the levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory (IL-4) cytokines in the blood serum of pregnant women at different stages of gestation: 18-20, 28-30, and 33- 38 weeks. The study involved 76 patients at risk of developing preeclampsia. Of these, 34 women developed preeclampsia, making up the main group, and 42 pregnant women had no symptoms of preeclampsia and made up the comparison group. The control group consisted of 28 somatically healthy women with a physiologically normal pregnancy. The average age of the examined patients with preeclampsia was 26.2±4.3 years, and in the group of pregnant women with normal pregnancy it was 25.8±4.7 years. The purpose of the study was to study the levels of cytokines IL-4, IL-6, IL-17A, and IL-18 in women with uncomplicated pregnancy and preeclampsia. These cytokines play an important role in the immune response and may be associated with the development of preeclampsia. The results of the study may help further understand the mechanisms of the disease and develop strategies for its prevention and management. The levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory cytokines (IL-4, IL-10) were studied in blood serum by ELISA using test systems of Vector-best JSC (Novosibirsk, Russia) in accordance with the manufacturer’s recommendations. Statistical processing of research results was carried out using variation statistics methods. The results are presented as the sample mean (M) and standard error (m). The significance of the differences in the mean values (P) of the compared indicators was assessed using the Student t test (t). A study conducted by the authors found the following patterns in interleukin (IL) levels in pregnant women at risk of developing preeclampsia (PE). The levels of IL-6, IL-17A, and IL-18 were significantly increased in pregnant women with PE. There was a tendency to decrease the levels of IL-4, and IL-10 in women at risk of developing preeclampsia. These findings may help guide further research and development of strategies to prevent and manage preeclampsia in pregnant women.

Experimental infection of ringtail possums (Pseudocheirus peregrinus) with Mycobacterium ulcerans, the agent of Buruli ulcer

Buruli ulcer (BU) is a necrotizing disease of skin and soft tissue caused by the bacterium Mycobacterium ulcerans (MU). In Australia, where the disease is emerging in new geographic areas and human case numbers are increasing, native possum species act as reservoir hosts. To better understand the life history of MU in one of its natural hosts, we conducted intra-dermal challenge of six wild caught, MU-naïve common ringtail possums (Pseudocheirus peregrinus). All six animals developed BU disease consistent with that observed in naturally infected ringtail possums. Time to ulceration varied between 49 and 77 days (mean = 61.8 days). Molecular evidence of systemic infection was detected in five animals and was supported by consistent histopathological findings in four animals. Pathological findings included random, multifocal, granulomatous hepatitis in four possums, one of which also had a mild, multifocal, interstitial granulomatous pneumonia. Acid-fast bacilli were only evident in inflammatory foci beyond the primary inoculation site in one possum. The ringtail possum model of MU infection is an important tool for the investigation of bacterial transmission dynamics, pathogenesis and immune response in a natural host. Data from this model may improve disease risk modelling and help identify intervention points to stop zoonotic transmission and disease spread.

Differential Host Gene Expression in Response to Infection by Different Mycobacterium tuberculosis Strains—A Pilot Study

Tuberculosis (TB) represents a global public health threat and is a leading cause of morbidity and mortality worldwide. Effective control of TB is complicated with the emergence of multidrug resistance. Yet, there is a fundamental gap in understanding the complex and dynamic interactions between different Mycobacterium tuberculosis strains and the host. In this pilot study, we investigated the host immune response to different M. tuberculosis strains, including drug-sensitive avirulent or virulent, and rifampin-resistant or isoniazid-resistant virulent strains in human THP-1 cells. We identified major differences in the gene expression profiles in response to infection with these strains. The expression of IDO1 and IL-1β in the infected cells was stronger in all virulent M. tuberculosis strains. The most striking result was the overexpression of many interferon-stimulated genes (ISGs) in cells infected with the isoniazid-resistant strain, compared to the rifampin-resistant and the drug-sensitive strains. Our data indicate that infection with the isoniazid-resistant M. tuberculosis strain preferentially resulted in cGAS-STING/STAT1 activation, which induced a characteristic host immune response. These findings reveal complex gene signatures and a dynamic variation in the immune response to infection by different M. tuberculosis strains.

Adeno‐associated virus vectors for gene therapy—focusing on melanoma

AbstractAdeno‐Associated Virus (AAV) vectors have been found to have great potential in the field of gene therapy due to their unique properties. These nonpathogenic vectors exhibit high tissue specificity, low immunogenicity, and sustained gene expression, enhancing their efficacy for targeted delivery. This review explores the application of AAV vectors in gene therapy. It introduces the application and development of AAV in hemophilia and Duchenne Muscular Dystrophy. The review also highlights the use of AAV vectors in melanoma gene therapy, focusing on four key areas: cancer growth intervention, targeting cancer cells, mediating immune responses, and modulating key signaling pathways. However, despite its many advantages, rAAV faces significant challenges, including host immune responses and biological barriers that limit its effectiveness. Such complexities need to be addressed; therefore, this review also discusses the application of several polymers, such as hydrogels, nanoparticles, and solid scaffolds, in the controlled delivery of AAV.