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T-cell-stimulating protein A elicits immune responses during meningococcal carriage and human disease.

In recognition of the need for immunological memory-inducing components for future Neisseria meningitidis group B vaccines, we previously searched the proteome of N. meningitidis and identified T-cell-stimulating protein A (TspA). This study was designed to confirm the immunogencity of TspA and to examine the subset of T-helper cell responses to the protein in patients and nasopharyngeal carriers. The tspA gene was reconstructed, cloned, and expressed in Escherichia coli, and the recombinant TspA (rTspA) protein was affinity purified. T-cell proliferative responses to rTspA were detected in th

Immunopotentiation by Natural Extracts: Mechanisms and Applications in Influenza Vaccine Adjuvant Development.

Despite the widespread use of seasonal influenza vaccines, their efficacy remains limited particularly among the elderly, immunocompromised individuals, and in the face of antigenically drifted or shifted viral strains. Traditional adjuvants enhance vaccine efficacy but may have limitations related to safety, tolerability, or restricted immune activation. Natural extracts derived from plants, marine organisms, fungi, and algae are gaining attention as novel adjuvants due to their ability to modulate both innate and adaptive immunity with low toxicity. This review highlights key natural compoun

TREM2 Regulates Microglial Activation via the ERK/p38 Signaling Pathway: Implications for the Pathogenesis of Experimental Autoimmune Uveitis.

PURPOSE: The purpose of this study was to investigate the role of the trigger receptor expressed on myeloid cell 2 (TREM2) in experimental autoimmune uveitis (EAU) and elucidate the mechanisms by which TREM2 modulated inflammation and microglial activation via key signaling pathways. METHODS: EAU mouse models and microglial cell BV2 inflammation models were established to explore TREM2 function. TREM2 expression in EAU retinas was detected using public databases and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RT-qPCR, Western blotting, enzyme-linked immunosorbent a

Innate-adaptive immune crosstalk: TLR2 expression and CD8+ memory T cell responses in leprosy.

Leprosy presents a clinical-immunological spectrum determined by the host immune response to Mycobacterium leprae. While paucibacillary (PB) patients mount a TH1-polarized response with effective bacillary control, multibacillary (MB) exhibit TReg/TH2 dominance and bacterial persistence. This study investigated TLR2/NF-κB-related immunophenotypic profiles in monocytes and their association with memory CD8+ T cell functional responses across the leprosy spectrum. Peripheral blood mononuclear cells from PB, MB, and healthy controls were stimulated with M. leprae antigen and analyzed by flow cyto

Peiminine modulates T cell-associated gene expression and inflammatory activity in experimental autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by immune-mediated hepatocellular injury and insufficient regulatory T cell (Treg) control. Despite the efficacy of corticosteroids and azathioprine, incomplete response, side effects, and relapse often limit treatment, underscoring the need for novel therapeutic strategies. To date, little is known about the potential of natural compounds in modulating T cell-related pathways in AIH. This study aimed to evaluate the therapeutic effects of peiminine, an alkaloid with reported anti-inflammatory and immunomodulatory

Болезни Увечье с возрастом в экспериментальной модели множественного склероза: роль иммунозенсии.

Начавшийся множественный склероз (MS) у пожилых людей соотносится с более высоким риском развития первичных прогрессивных MS, ускорения перехода к вторичным прогрессивным MS и увеличения накопления инвалидности. Это явление может быть связано с возрастными изменениями в иммунной системе: с возрастом иммунная система проходит процесс, называемый иммунной сенсацией, который характеризуется снижением функции как врожденной, так и адаптивной иммунной реакции. Такое снижение может привести к снижению способности контролировать воспаление и восстанавливать поврежденные ткани. Кроме того, пожилые люд

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… Th1 cells were initially considered to be responsible for EAE and MS immunopathogenesis, as IFN‐γ was abundant in CNS lesions (Merrill et al.  1992 ; Traugott and Lebon  1988 ) and the administration of this cytokine to MS patients exacerbated the disease (Panitch et al.  1987 ). … Th17 cells demonstrate substantial developmental plasticity after their commitment towards Th1 cells (Lee et al.  2009 ) and IFN‐γ and IL‐4 negatively regulate Th17 development (Park et al.  2005 ), these facts may explain the higher Th1/Th17 ratio found along the disease with age. …

Non-clinical evaluation of local and systemic immunity induced by different vaccination strategies of the candidate tuberculosis vaccine M72/AS01.

A new efficacious tuberculosis vaccine targeting adolescents/adults represents an urgent medical need. The M72/AS01E vaccine candidate protected half of the latently-infected adults against progression to pulmonary tuberculosis in a Phase IIb trial (NCT01755598). We report that three immunizations of mice, two weeks apart, with AS01-adjuvanted M72 induced polyfunctional, Th1-cytokine-expressing M72-specific CD4+/CD8+ T cells in blood and lungs, with the highest frequencies in lungs. Antigen-dose reductions across the three vaccinations skewed pulmonary CD4+ T-cell profiles towards IL-17 expres

A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection.

Influenza pandemics pose public health threats annually for lacking vaccine that provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens that induce cross-protective antibody responses with epitopes that activate cross-protective T cell responses might be an attractive strategy for developing a universal vaccine. In this study, we constructed a recombinant protein named NMHC that consists of influenza viral conserved epitopes and a superantigen fragment. NMHC promoted the maturation of bone marrow-derived dendritic cells and induced CD4+ T cells to

In Vitro Evaluation of Immunogenicity of Recombinant OMP25 Protein Obtained from Endemic Brucella abortus Biovar 3 as Vaccine Candidate Molecule Against Animal Brucellosis.

BACKGROUND: Brucellosis is a zoonotic disease that causes serious economic losses due to factors, such as miscarriages and decreased milk yield in animals. Existing live vaccines have some disadvantages, so effective vaccines need to be developed with new technological approaches. OBJECTIVE: The primary objectives of this study were the expression and purification of recombinant Omp25 fusion protein from B. abortus, and the evaluation of the effect of the Omp25 protein on cell viability and inflammatory response. METHODS: The omp25 gene region was amplified by a polymerase chain reaction and

Heterologous prime-boost immunizations with chimpanzee adenoviral vectors elicit potent and protective immunity against SARS-CoV-2 infection.

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed to tackle the COVID-19 global pandemic. Here, we describe the development of chimpanzee adenovirus serotypes 6 and 68 (AdC6 and AdC68) vector-based vaccine candidates expressing the full-length transmembrane spike glycoprotein. We assessed the vaccine immunogenicity, protective efficacy, and immune cell profiles using single-cell RNA sequencing in mice. Mice were vaccinated via the intramuscular route with the two vaccine candidates using prime-only regimens or heterologous prime-bo

Thyroid autoimmunity and its association with cellular and humoral immunity in women with reproductive failures.

PROBLEM: thyroid autoimmunity (TAI), which is T helper (Th)1-cell-mediated autoimmunity to thyrocytes, is associated with increased risk of miscarriages and highly prevalent in women with infertility. We aim at investigating the prevalence of TAI in women with recurrent spontaneous abortions (RSA) or unexplained infertility (UI) and its relationship with cellular and humoral immune abnormalities. METHOD OF STUDY: prevalence of antiphospholipid antibodies, anti-nuclear antibody, other non-organ-specific antibodies (NOSAs; anti-dsDNA, anti-ssDNA, anti-histone, anti-Scl70), peripheral blood natu

The human T cell response to myelin oligodendrocyte glycoprotein: a multiple sclerosis family-based study.

Myelin oligodendrocyte glycoprotein (MOG) is an encephalitogenic myelin protein and a likely autoantigen in human multiple sclerosis (MS). In this work, we describe the fine specificity and cytokine profile of T cell clones (TCC) directed against MOG in three nuclear families, comprised of four individuals affected with MS and their HLA-identical siblings. TCC were generated from PBMC by limiting dilution against a mixture of eleven 20-mer overlapping peptides corresponding to the encephalitogenic extracellular domain of human MOG (aa 1-120). The frequency of MOG peptide-reactive T cells was s

Multiple pathways to induction of virus-induced autoimmune demyelination: lessons from Theiler's virus infection.

Infection of SJL mice with wild-type BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) leads to CD4(+)T cell-mediated CNS demye … the epitope develop an early onset demyelinating disease mediated by activated PLP139-151-specific Th1 cells. The autoimmune nature of this early-onset demyelinating disease is shown by the fact that induction of tolerance to the PLP139-151 peptide prevents clinical disease and associated PLP139-151-specific T cell responses without affecting T cell reacti …

The role of lymphotoxin in pathogenesis of polymyositis.

Polymyositis (PM) is a cell-mediated autoimmune disease. Perforin (PF), Fas ligand (FasL) and TNF-alpha are considered to be important factors in cytotoxic T lymphocyte-mediated cell injury, and several studies have established a role of lymphotoxin (LT) in T helper type 1 (Th1)-induced cell-mediated autoimmune diseases. In the present study, to determine how LT, PF and FasL are involved in the pathogenesis of PM, we used immunohistochemical staining (IHC), reverse transcription polymerase chain reaction (RT-PCR), and in situ hybridization (ISH) on muscle specimens from patients with PM, amyot

Influence of resistant and susceptible genotype, IL-1, and lymphoid organ on Trichinella spiralis-induced cytokine secretion.

The relative importance of cell-mediated inflammatory responses and antibody-mediated responses in controlling parasitic helminth infection is debated. To study the relationship between these responses and resistance or susceptibility to primary Trichinella spiralis infection, we infected resistant AKR mice and susceptible B10.BR mice and analyzed the lymphokines IL-2, IFN-gamma, and IL-5 produced by their T cells as a function of time and lymphoid organ. IL-2-secretors occurred maximally between days 3 and 6 postinfection, whereas IL-5-secretors peaked between days 6 and 9. Previously, we fou

Icariin Modulates the Reproductive-Immune Axis: Molecular Insights and Therapeutic Potential.

The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated from Epimedium species (Horny Goat Weed), has a long-standing traditional use for "invigorating yang," which modern research attributes to its reproductive function-enhancing properties. This review synthesizes emerging evidence that the beneficial

Deletion of steD gene and yejAE operons in LPS-deficient Salmonella elicits strong t cell immunity and complete protection against homologous serotypes.

Non-typhoidal Salmonella (NTS) infections are a major cause of foodborne illness worldwide, and rising antimicrobial resistance underscores the need for effective vaccines. Live attenuated Salmonella strains have potential, but developing an effective vaccine remains a challenge. In this study, we built on the previously constructed attenuated Salmonella Typhimurium strain RAST002, which carries deletions of manA and steD, by introducing a yejAE operon deletion to generate RAST003, aiming to further enhance immune responses. Oral immunization with this single strain induced robust systemic IgG

Sphingolipid Metabolism in the Pathogenesis of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disorder, characterized by progressive lymphocytic infiltration, follicular destruction, tissue fibrosis, and an elevated risk of thyroid carcinoma. While the precise mechanisms underlying HT remain incompletely defined, emerging evidence implicates dysregulated sphingolipid (SPL) metabolism, particularly the sphingosine-1-phosphate (S1P) signaling axis, as a central contributor to disease pathogenesis. S1P, a bioactive lipid mediator, integrates metabolic and immunological cues to regulate immune cell trafficking, cytokine pro

Antileishmanial potential of immunomodulator gallic acid against experimental murine visceral leishmaniasis.

The menace of the enfeebling disease leishmaniasis prevails due to the inaccessibility of effective vaccine and chemotherapy. Hence in the pursuit of finding novel alternative options with reasonable efficacy, immunomodulation, leishmanicidal activity and fewer side effects, screening of compounds from natural sources is needed. This study was focused on in vitro and in vivo antileishmanial screening of gallic acid (GA) against Leishmania donovani infection in BALB/c mice. GA showed in vitro parasiticidal activity and IC50  value of 19.59 ± 0.74 µg/ml and is able to arrest cell cycle at the su

Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren's syndrome.

Mesenchymal stem cell (MSCs) transplantation has been used to treat Sjögren's syndrome (SS) based on the immunoregulatory properties of MSCs. However, the effectiveness need improving and its underlying intrinsic mechanisms remain largely unknown. Here, we show that Id3 is upregulated in bone marrow-derived MSCs (BMMSCs) isolated from NOD/ShiLtJ mice, a widely used SS model, compared with ICR mice as control, suggesting that it functions in SS development and therapy. Transplantation of Id3-deficient BMMSCs rescues salivary gland function more effective than wild-type BMMSCs in NOD/ShiLtJ mice