Molecular Immunology

One of the major reasons behind the limited success of vaccine candidates against all forms of leishmaniasis is the inability of parasitic antigens to induce robust cell-mediated immunity and immunological memory. Here we find, for the first time, that the adjuvantation of whole-killed Leishmania vaccine (Leishvacc) with anti-CD200 and anti-CD300a antibodies enhances CD4+ T cells mediated immunity in vaccinated mice and provides protection against wild-type parasites. The antibody adjuvantation, either alone or with a TLR4 agonist monophosphoryl A (MPL-A), induced the production of pro-inflammatory cytokines viz...

The NLRP3 inflammasome is involved in many inflammatory diseases. Its activity must be strictly controlled to alleviate the inflammatory process. Autophagy plays a protective role in the negative regulation of NLRP3 inflammasome activation. However, the regulatory mechanism of autophagy controlling NLRP3 inflammasome activation remains to be further investigated. Here, we showed that in NRK-52E cells, lipopolysaccharide (LPS) and ATP stimulation significantly decreased mitochondrial membrane potential, increased ROS production and mtDNA copy number in cytosol...

Plasmodium vivax's biological complexity has restricted in vitro culture development for characterising antigens involved in erythrocyte invasion and their immunological relevance. The murine model is proposed as a suitable alternative in the search for therapeutic candidates since Plasmodium yoelii uses homologous proteins for its invasion. The AMA-1 protein is essential for parasite invasion of erythrocytes as it is considered an important target for infection control. This study has focused on functional PyAMA-1 peptides involved in host-pathogen interaction; the protein is located in regions under negative selection as determined by bioinformatics analysis...

Pulpitis is a chronic inflammatory process that greatly affects the physical, mental health and life quality of patients. Human dental pulp cells (hDPCs) are essential components of dental pulp tissue and play a significant role in pulpitis. Lipopolysaccharide (LPS) is an initiator of pulpitis and can induce the production of inflammatory cytokines in hDPCs by activating p38 MAPK and NF-κB signaling pathways. Importin7 (IPO7), a member of the importin-β family, is widely expressed in many tissues...

Acetaminophen (APAP) is a common antipyretic and analgesic drug that can cause long-term liver damage after an overdose. Non-alcoholic fatty liver disease (NAFLD) increases susceptibility to APAP. In NAFLD, excessive accumulation of lipids leads to an abnormal increase in hypoxia-inducible factor-1α (HIF-1α). Caveolin-1 (CAV1) may protect against NAFLD by inhibiting HIF-1α. This research aimed to determine whether CAV1 could attenuate APAP-exacerbated liver injury in NAFLD by inhibiting oxidative stress involving HIF-1α...

miR-495 is aberrantly expressed and affects the progression of inflammation in various diseases. However, the mechanisms of miR-495 in bovine endometritis remain largely unknown. This study investigated the mechanism of miR-495 in lipopolysaccharide (LPS)-induced bovine endometritis and pyroptosis and found that miR-495 inhibits NLRP3 inflammasome activation and inflammatory immune responses in endometritis tissue and cell models. Bovine endometrial epithelial cells (BENDs) were treated with 10 μg/mL LPS to establish a cell inflammatory model...

Microglia are the first-line defenders against invading pathogens in the brain whose activation mediates virus clearance and leads to neurotoxicity as well. This work studies the role of Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1)/vacuole membrane protein 1 (VMP1) interaction in the activation of microglia and neuroinflammation following herpes simplex virus 1 (HSV-1) infection. Aberrantly expressed genes after HSV-1 infection were screened by analyzing the GSE35943 dataset. C57BL/6J mice and mouse microglia BV2 were infected with HSV-1 for in vivo and in vitro assays...

There is a high incidence of fractures in clinical practice and therapy. The repairment of critical size defects in the skeletal system remains a huge challenge for surgeons and researchers, which can be overcame by the application of bone tissue-engineered biomaterials. An increasing number of investigations have revealed that the immune system plays a vital role in the repair of bone defects, especially macrophages, which can modulate the integration of biomaterials and bone regeneration in multiple ways...

Evidence concerning the individual differences in neutralizing antibody responses after receiving the COVID-19 vaccine remains lacking. In this study, we collected the serum and Peripheral blood mononuclear cells(PBMC) of 16 subjects who had never suffered from COVID-19 before during the course of two vaccine doses. Microneutralization assay is used to determine the immune response intensity of vaccine subjects. we revealed the change trend of TCR diversity using T cell receptor (TCR) sequencing. Then, we analyzed the correlation between HLA class II allele frequencies and the intensity of immune response...

Glucocorticoids have been widely used in the treatment of ulcerative colitis, but not all patients benefit from this therapy due to hormone resistance. Mir-150-5p has been reported to enhance the efficacy of glucocorticoids, and low serum mir-150-5p expression has been linked to glucocorticoid resistance in ulcerative colitis patients. The aim of this study was to elucidate the mechanisms of mir-150-5p regulation on glucocorticoid resistance. An ulcerative colitis mouse model was used to evaluate changes in ulcerative colitis symptoms, inflammatory factors, and glucocorticoid resistance-related gene expression...

The development of Immune checkpoint blockade(ICB) therapy and BRAF- and MEK-targeted therapies has reshaped the survival outcomes of the patients with advanced melanoma. PD-1/PD-L1 blockade was an approved strategy in melanoma treatment. Here we design a PD-L1 xCD3 nanobody as a novel bispecific T cell engager (BiTE) in treating PD-L1 overexpression melanoma. BiTE PD-L1×CD3 Nb was predicted to bind near a large acidic surface on CD3-ε similar to UCHT1-scFv antibody based on alpha-fold and molecular docking...

Understanding COVID-19 exposure differences among Healthcare Workers (HCWs) across various healthcare units is crucial for their protection and effective management of future outbreaks. However, comparative data on COVID-19 among HCWs in different healthcare units are scarce in Brazil. This study evaluated the relationship between SARS-CoV-2 infection and workplaces in HCWs from three distinct healthcare settings in Brazil. It also examined COVID-19 symptom dynamics reported by them. The cohort comprised 464 HCWs vaccinated with two doses of CoronaVac and a BNT162b2 booster from different institutions: Primary Health Care Units (PHCUs), Emergency Care Units (ECUs), and Hospitals...

Psoriasis is one of the most common immune-mediated chronic inflammatory skin diseases, involving excessive proliferation of keratinocyte and infiltration of immune cells. There are many factors that cause the onset of psoriasis, so the exact pathogenesis of psoriasis still needs to be determined. High mobility group box-1 (HMGB1), a pro-inflammatory cytokine, is closely related to the pathogenesis of various inflammatory diseases. However, there are few studies investigating the effects of HMGB1 on inflammatory dermatoses...

Cytotoxic T lymphocytes (CTLs) play protective roles in immunity against tuberculosis (TB) infection by strongly inhibiting intracellular mycobacterial growth. In TB infection, the impairing mechanism of CTLs function remains unclear. In this study, we identified that the cytotoxic granule molecules expression levels of perforin (PRF) and granulysin (GNLY) in CD3+ and CD8+ CTL cells were significantly depressed in TB patients compared to those in healthy donors. The frequencies of T-CTLs, co-expressing granzyme B (GZMB), PRF and GNLY, were obviously decreased in TB patients...

Hepatocellular carcinoma (HCC) remains one of the most common and highly fatal malignancies in humans worldwide with increasing prevalence and limited therapeutic options. For many decades, many researchers have attempted to find effective curative methods for HCC and great strides have been made. GPC3 is overexpressed in HCC, but not in normal liver, making it a rational immunotherapeutic target for HCC. GC33, a humanized mAb directed against GPC3, is a safe and well-tolerated therapy choice for patients with HCC, which tested in a phase I trial in advanced HCC patients...

Ligand recognition by the human α/β T-cell antigen receptor (TCR) heterodimer protein, unlike the surface immunoglobulin (sIg) B-cell receptor, is not governed by relative binding affinity. Its interaction with the peptide (p) plus major histocompatibility complex (MHC) protein (abbrev. pMHC) likely involves some different molecular mechanism linking pMHC binding to T-cell functions. Recent analytical geometry of TCR:pMHC-II solved crystallographic structures (n = 40) revealed that each variable (V)-domain is bound in similar, yet mathematically unique orientations to its target pMHC groove...

BACKGROUND: The SOCS proteins act as suppressors of cytokine signaling by impeding certain signaling pathways. SOCS5, a constituent of the SOCS family, has been associated with the management of allergic reactions, primarily by impeding the signaling of interleukin-4 (IL-4), which is known to have a cardinal function in accelerating the development of an allergic reaction. The key goal of our research was to explore the probable ramifications of the SOCS5 single nucleotide polymorphism (SNP) namely rs41379147 on the expression of SOCS5 mRNA and serum IL-12 levels, as well as to analyze the interaction between SOCS5 genotypes and various clinicopathological parameters in atopic diseases...

It is found that HDAC3 may be a potential therapeutic target for intestinal related diseases. At present, the role and mechanism of HDAC3 in the pathogenesis of severe acute pancreatitis (SAP) have not been reported, which needs to be further explored. The SAP mouse model was established and the expression of HDAC3 was detected by immunohistochemistry. H&E staining showed the intestinal pathological state of SAP mice. The expression of HDAC3 was measured by real-time quantitative PCR (RT qPCR) and Western blot...

Vacuolar-type H+ -ATPase (V-ATPase) critically controls phagosome acidification to promote pathogen digestion and clearance in macrophage. However, the specific subunits of V-ATPase have been evidenced to play contradictory functions in inflammatory cytokines generation and secretion exposure to external bacterial or LPS stimulation. Therefore, identifying the unique function of the separate subunit of V-ATPase is extremely important to regulate macrophage function. Here, we found that D-mannose, a C-2 epimer of glucose, suppressed ATP6V1B2 lysosomal translocation to inhibit V-ATPase activity in macrophages, thereby causing the scaffold protein axis inhibitor protein (AXIN) recruitment to lysosomal membrane and AMPK activation...

BACKGROUND: Overweight and obesity are related to an increased risk of asthma. The effect of platycoside E (PE) on obesity-related asthma remains unknown. METHODS: To mimic obesity-related asthma conditions in vivo, C57BL/6 mice were exposed to a high-fat diet (HFD) and challenged with ovalbumin (OVA). PE was administrated intraperitoneally during the OVA treatment. Body weight was measured at 8th week before PE treatment and after sacrificing the mice. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated...