Copper, a transition metal, plays crucial roles in various physiological functions, including those of the nervous and immune systems. Dysregulation of copper homeostasis is linked to several diseases, such as neurodegenerative diseases. Since dysfunctional microglial immunity can also contribute to such diseases, we investigated the role of copper in microglial immunity. Currently, the roles of copper in microglial immunity are considered complex and multifaceted, with both anti- and pro-inflammatory effects having been proposed. In the current study, we found that both increased and decreased copper levels suppressed lipopolysaccharide (LPS)-mediated inflammation in microglial cells, as determined by RT-qPCR analysis. RNA sequencing (RNA-seq) analysis confirmed that increased copper levels reduced the inflammatory response to LPS; however, it also showed that decreased copper levels affected genes involved in cell proliferation, transcription, and autophagosome regulation. These findings suggest that copper is vital for maintaining normal immune functions in microglia, and that both copper excess and deficiency can disrupt microglial immunity.

To evaluate the predictive value of NKG2A natural killer (NK) cells in identifying patients at risk of developing severe COVID-19 and assess the therapeutic potential of NKG2A blockade in restoring NK cell antiviral activity.

To investigate the role of IL33/HIF1α/VEGF in lung tissue injury caused by intermittent hypoxia (IH) model in mice, and to reveal its possible mechanisms.

Colorectal cancer (CRC) requires effective preventive measures due to its high prevalence, mortality rate, and impact on patients' lives. Therefore, this study aimed to assess the immunomodulatory effects of α-tocopherol (α-TOC) within the tumor microenvironment (TME) of CRC using a co-culture model.

This study aims to investigate the role of the WNT5A signaling pathway in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and uncover the impact of WNT5A on cellular function and signal transduction through proteomic and phosphoproteomic analyses.

Malaria is an important and serious parasite-induced disease associated with severe anemia and multiple organ failure (MOF) that can be lethal in humans. We explored the contribution of the terminal pathway of complement in a mouse model of malaria-induced lethal MOF following infection with Plasmodium (P.) bergei.

Recent research has underscored NLRX1's role in modulating hepatic immune responses. However, its function in Kupffer cells (KCs) during acute rejection (AR) post-liver transplantation is not well elucidated, and the mechanisms driving hepatic AR require deeper investigation. Our study found that NLRX1 expression was markedly reduced in hepatic AR models, both in vivo and in vitro. NLRX1 overexpression significantly dampened the activation of the MAPK and IKK pathways, leading to decreased cytokine secretion and mitigated liver damage and apoptosis. In contrast, NLRX1 downregulation intensified these adverse effects. Further mechanistic studies indicated that NLRX1's interaction with TRAF6 was crucial for its anti-inflammatory effects, which could be nullified by TRAF6 blockade. Moreover, in vitro assays showed that NLRX1 could drive KCs to transition from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype via the PI3K/Akt pathway. Overall, our results imply that targeting NLRX1 in conjunction with mTOR could be a viable approach to prevent hepatic AR, and suggest potential cross-talk between TRAF6-dependent inflammatory suppression and PI3K/Akt-mediated M2 polarization that requires further validation.

We investigated circulating and urinary inflammatory mediators and extracellular vesicles (EVs) in association with clinical and laboratory findings during the post-COVID-19 (coronavirus disease 2019) period.

OX40 is a typical member of the co-stimulatory molecule family. The signals generated by its binding to OX40L have a synergistic effect, regulating T cell proliferation, differentiation, and influencing cytokine secretion. This study aimed to evaluate the role of OX40 in regulating the progression of liver fibrosis induced by CCL4-induced inflammation.

Human BK polyomavirus (BKV) infection is a dangerous pathogenic factor in kidney transplant recipients (KTRs) due to the use of immunosuppressive drugs, which can cause damage to the transplanted kidneys after reactivation. BKV interacts with transcription factors that regulate the expression of genes involved in the immune system, which can cause kidney failure or transplant rejection due to tumorigenic antigens.

This study had two primary objectives. First, we aimed to investigate whether differential expression of the chemokine receptor CXCR4 on CD4 T lymphocytes could serve as a distinguishing immunological feature between pediatric patients with severe Mycoplasma pneumoniae pneumonia (SMPP) and those with on- Non-severe MPP. Second, we sought to explore the therapeutic potential of the JAK inhibitor Tofacitinib in MPP by examining its effects on CXCR4 pathway modulation, using both clinical observations and experimental validation through an established animal model of MPP.

Women and men are different on many biological levels. Mounting evidence is now recognized that even the immune system has some significant sex differences, which are mainly cell mediated. This study investigated sex-specific differences in function and regulation of polymorphonuclear neutrophil granulocytes (PMNs) in male and female healthy human donors to gain a deeper understanding of the immune response and potential sex-specific dimorphism in immunology.

The liver is among the organs most frequently damaged during sepsis, and sepsis-induced liver injury is an independent risk factor for early patient mortality. Ferroptosis has been implicated in sepsis-related organ dysfunction; however, its role in sepsis-induced liver injury remains unclear. This study aimed to investigate the role and underlying mechanisms of ferroptosis in sepsis-associated liver injury.

Gamma radiation (γR) influences cytokine regulation, with high doses (HD) producing marked biological effects under both controlled and accidental exposure scenarios. This study investigates the immunological responses to γR at doses of 2, 3, and 5 Gray (Gy) by examining T-cell receptor (TCR) mRNA expression, serum levels of Interleukin-10 (IL-10), Transforming Growth Factor-β (TGF-β), and Nitric Oxide (NO), as well as hematological parameters. These effects were compared between days 1 and 4 post-irradiation. Forty-eight male rats were randomly allocated into eight groups (six rats each), with Groups I and V serving as non-irradiated controls. Groups II-IV and Groups VI-VIII received whole-body γ-irradiation at doses of 2, 3, and 5 Gy, respectively. On days 1 and 4 after exposure, reverse transcription quantitative PCR (RT-qPCR) and standard hematological techniques were employed to assess gene expression, cytokine levels, hemoglobin concentration, hematocrit percentage, blood cell counts, and organ weights. This study demonstrates that high-dose γ-radiation (2-5 Gy) significantly (P < 0.05) increases TCR mRNA expression, hematological indices, and lymphoid organ weights, while IL-10 declines (P < 0.05), and TGF-β and nitric oxide levels are markedly elevated. Despite these observations, the null hypothesis was accepted for both time points (P > 0.05), indicating that there were no statistically significant differences across specific parameters. The observed inverse correlation between radiation exposure and lymphoid organ development supports the role of γR in altering immune-regulatory cytokines. Ultimately, higher γR doses tend to produce more pronounced immunological alterations, regardless of the intent of exposure.

Human leukocyte antigen (HLA)-E as a non-classical HLA class I molecule interacting with NK and T cell receptors may activate or inhibit immune responses. These reactions can impact reproductive success because HLA-E is expressed by trophoblast cells. In this study, we investigated rs1264457 A/G HLA-E polymorphism in couples with reproductive failures such as recurrent implantation failure (RIF) after in vitro fertilization (IVF), recurrent spontaneous abortion (RSA), and sporadic spontaneous abortion (SSA) after natural conception. Furthermore, we investigated the role of the soluble HLA-E isoform (sHLA-E) in women's plasma and seminal plasma of men participating in IVF procedures.

The ability of Natural Killer (NK) cells, to generate memory-like responses against viruses including - HIV, opened up possibility of their application as immune therapy. We attempted to generate memory-like NK cells from HIV exposed and unexposed primary NK cells. The PBMCs of HIV uninfected and infected individuals (LTNPs, ART experienced and with progressive disease) were preactivated with cytokine cocktail (CC) of IL12, IL 15 and IL 18 with or without HIV-1 Env C or only IL 15 and restimulated with CC + HIV-1 Env C after seven days' rest. The CD56+ NK cells from the cultures were assessed for IFN-γ, TNF-α, and perforin secretion and expression of CD107a using multiparametric flow cytometry. Higher functionality was observed in case of pre-activation with CC with or without HIV-1 Env C as compared to only Il 15 across study groups. However, the functionality of the generated memory -like NK cells was significantly higher in case of LTNPs and the ART experienced individuals only. Low frequency of functional NK cells generated from HIV unexposed NK cells indicate probable specificity to HIV. The memory-like NK cells from ART experienced individuals generated after CC and CC+ HIV-1C preactivation showed good proliferating ability and also an ability to lyse the allogenic HIV infected CD4+ T cells. This work highlighted that HIV specific memory-like NK cells can be generated from the NK cells of HIV infected individuals with robust immune status after pre-activation with cytokine cocktail with or without HIV-1C. Although preliminary, these findings suggest that memory-like NK cells could have potential for use in immunotherapy aimed at clearing viral reservoirs.

Klebsiella pneumoniae (Kp) infection has high global complication and mortality rate. Programmed cell death ligand 1 (PD-L1) is important for immune evasion in tumorigenesis, however, with unclear mechanism in Kp infection. This study aims to explore the role and potential mechanisms of PD-L1 in Kp-infected mouse mononuclear macrophages RAW264.7 cells. Here, RAW264.7 cells were infected with classical Kp (cKp) and highly virulent Kp (hvKp), and transfected with PD-L1 knockdown. Subsequently, to investigate the effect of PD-L1 on the activation of CD4 T cells, a co-culture system of RAW264.7 and CD4 T cells was established. In RAW264.7 cells infected with Kp, PD-L1 knockdown reduced apoptosis and necrosis, with lower Bax, Cleaved Caspase 3, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLKL expression. Meanwhile, phagocytic activity and phagocytic index were enhanced, with increased Kp count. Furthermore, PD-L1 knockdown led to the activation of RAW264.7 cells, which participated in immune regulation, accompanied by higher levels of IL-1β, IL-6, TNF-α, MHC II, CD80, and CD86. Following co-culture of RAW264.7 and CD4 T cells, PD-L1 knockdown reversed the effect of Kp infection to promote CD4 T cell activation, as evidenced by decreased apoptosis and elevated IFN-γ, TNF-α, and IL-2 levels. This result preliminarily demonstrated that PD-L1 expression may be involved in antigen presentation in RAW264.7 cells with Kp infection. In conclusion, in Kp-infected RAW264.7 cells, PD-L1 mediates the increased apoptosis, necrosis, inflammatory responses, and CD4 T cell activation, as well as inhibition of phagocytosis, and may be involved in antigen presentation, offering new therapeutic targets for Kp infection.

Anti-interferon gamma (IFN-γ) autoantibodies (AIGAs) are linked to opportunistic infections in adult-onset immunodeficiency (AOID). These autoantibodies, particularly those recognizing the C-terminal linear epitope (P128-143) and B27 epitope, block IFN-γ functions in monocytes, contributing to disease. In a retrospective analysis of residual plasma from 45 AOID patients, we confirmed the presence of AIGAs by indirect ELISA and evaluated their capacity to neutralize IFN-γ-induced MHC-II expression. All samples showed neutralizing capability, with varying epitope recognition: 10 samples had AIGAs which recognize both epitopes, 7 had B27 epitope-recognizing AIGAs, 12 had P128-143 epitope-recognizing AIGAs, and 16 had neither. Inhibition levels ranged from 36.5 % to 91.6 %. Five representative samples containing at least B27 epitope-recognizing AIGAs could inhibit guanylate binding protein 5 (GBP5) expression, crucial for pathogen killing. Additionally, high levels of neutralizing AIGAs persisted in patients with active and stable diseases. Overall, the data underscore the relationship between neutralizing AIGA levels, population characteristics, and persistence of AIGAs with monocyte dysfunction and disease outcome.

We studied plasma levels of complement system factors C1q, C2, C3, C3b, C4, C4b, C5, C5a, C9 of 84 patients with ischemic stroke within 24 h from onset of symptoms and on seventh day after admission, using Luminex immunoassay. C1q, C2, C3, C3b, C4, C4b, C5, C5a levels were significantly lower at Day 7, compared to Day 1. Patients with poor outcome (NIHSS ≥16 or death) had significantly higher C9 levels at both time points, and higher C2, C5 and C5a levels on Day 7 than the rest of the group. C2, C5, C5a and C9 correlated with final NIHSS score at both time points. Conclusions: Plasma levels of complement change dynamically within first days of the acute phase of ischemic stroke. Higher baseline C9 is associated with worse outcome in acute phase of ischemic stroke.

Infectious diseases remain a significant cause of mortality and morbidity worldwide. Complement is a critical component in the defense against pathogens and despite their great differences, viruses, bacteria, fungi, and protists have all developed similar mechanisms of evasion from the human complement system. Using examples from four microbial groups (viruses, bacteria, fungi and protists), this review expands on examples of these different mechanisms of evasion. The mechanisms are grouped as (A) avoidance of recognition, (B) avoidance of eradication, (C) avoidance of activation and function, or (D) use of the complement proteins for entry into the host, in accordance with the classification initially proposed in 1999. Furthermore, this review will expand on novel descriptions of complement evasion, for example involving intracellular complement. Taken toge complement evasion is an essential tool used by pathogens not only in a defensive manner, protecting the pathogen from the host, but can also employed in an aggressive manner to aid the invasion of the host. Understanding these mechanisms has already influenced diagnostic and therapeutic tools, including vaccine development, and a further expansion of evasion molecules as biomarkers, vaccines or targets for therapy appears likely in the future.

The ongoing promotion and administration of vaccines play a critical role in the global effort to eradicate poliovirus. The Monkey Neurovirulence Test (MNVT) is an essential method for evaluating the neurovirulence of viruses in both the Oral Attenuated Live Poliovirus Vaccine (OPV) and the Sabin Inactivated Poliovirus Vaccine (sIPV) to ensure they meet required safety standards. The "4-level scoring method" recommended by the World Health Organization (WHO) has served as a key pathological evaluation criterion in this test. However, its lack of scoring granularity often leads to subjective interpretation discrepancies among evaluators, which compromises the consistency and reliability of the MNVT results. To address these limitations, we have mapped the primary neuronal nuclei in monkey tissue sections and analyzed viral-induced damage distribution. As a result, we developed an Enhanced 4-Level Scoring System (integrating precise anatomical mapping and quantitative lesion analysis), which minimizes evaluator bias and significantly improves scoring stability and consistency.