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1.
Front Immunol ; 15: 1285785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433833

RESUMO

Introduction: Enteric infections are a major cause of under-5 (age) mortality in low/middle-income countries. Although vaccines against these infections have already been licensed, unwavering efforts are required to boost suboptimalefficacy and effectiveness in regions that are highly endemic to enteric pathogens. The role of baseline immunological profiles in influencing vaccine-induced immune responses is increasingly becoming clearer for several vaccines. Hence, for the development of advanced and region-specific enteric vaccines, insights into differences in immune responses to perturbations in endemic and non-endemic settings become crucial. Materials and methods: For this reason, we employed a two-tiered system and computational pipeline (i) to study the variations in differentially expressed genes (DEGs) associated with immune responses to enteric infections in endemic and non-endemic study groups, and (ii) to derive features (genes) of importance that keenly distinguish between these two groups using unsupervised machine learning algorithms on an aggregated gene expression dataset. The derived genes were further curated using topological analysis of the constructed STRING networks. The findings from these two tiers are validated using multilayer perceptron classifier and were further explored using correlation and regression analysis for the retrieval of associated gene regulatory modules. Results: Our analysis reveals aggressive suppression of GRB-2, an adaptor molecule integral for TCR signaling, as a primary immunomodulatory response against S. typhi infection in endemic settings. Moreover, using retrieved correlation modules and multivariant regression models, we found a positive association between regulators of activated T cells and mediators of Hedgehog signaling in the endemic population, which indicates the initiation of an effector (involving differentiation and homing) rather than an inductive response upon infection. On further exploration, we found STAT3 to be instrumental in designating T-cell functions upon early responses to enteric infections in endemic settings. Conclusion: Overall, through a systems and computational biology approach, we characterized distinct molecular players involved in immune responses to enteric infections in endemic settings in the process, contributing to the mounting evidence of endemicity being a major determiner of pathogen/vaccine-induced immune responses. The gained insights will have important implications in the design and development of region/endemicity-specific vaccines.


Assuntos
Proteínas Hedgehog , Vacinas , Imunomodulação , Imunidade , Expressão Gênica
2.
Front Immunol ; 15: 1362996, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426088

RESUMO

An increase in the extracellular concentration of ATP as a consequence of cellular stress or cell death results in the activation of immune cells. To prevent inflammation, extracellular ATP is rapidly metabolized to adenosine, which deploys an anti-inflammatory signaling cascade upon binding to P1 receptors on immune cells. The ectonucleotidases necessary for the degradation of ATP and generation of adenosine are present on the cell membrane of many immune cells, and their expression is tightly regulated under conditions of inflammation. The discovery that extracellular vesicles (EVs) carry purinergic enzyme activity has brought forward the concept of EVs as a new player in immune regulation. Adenosine-generating EVs derived from cancer cells suppress the anti-tumor response, while EVs derived from immune or mesenchymal stem cells contribute to the restoration of homeostasis after infection. Here we will review the existing knowledge on EVs containing purinergic enzymes and molecules, and discuss the relevance of these EVs in immune modulation and their potential for therapy.


Assuntos
Adenosina , Vesículas Extracelulares , Humanos , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Imunidade , Vesículas Extracelulares/metabolismo , Inflamação
3.
Front Immunol ; 15: 1341390, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426089

RESUMO

The tumor microenvironment is composed of tumor cells, stromal cells and leukocytes, including innate and adaptive immune cells, and represents an ecological niche that regulates tumor development and progression. In general, inflammatory cells are considered to contribute to tumor progression through various mechanisms, including the formation of an immunosuppressive microenvironment. Macrophages and neutrophils are important components of the tumor microenvironment and can act as a double-edged sword, promoting or inhibiting the development of the tumor. Targeting of the immune system is emerging as an important therapeutic strategy for cancer patients. However, the efficacy of the various immunotherapies available is still limited. Given the crucial importance of the crosstalk between macrophages and neutrophils and other immune cells in the formation of the anti-tumor immune response, targeting these interactions may represent a promising therapeutic approach against cancer. Here we will review the current knowledge of the role played by macrophages and neutrophils in cancer, focusing on their interaction with other immune cells.


Assuntos
Neoplasias , Neutrófilos , Humanos , Macrófagos , Imunidade , Imunoterapia , Microambiente Tumoral
4.
Actas Esp Psiquiatr ; 52(1): 1-9, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38454896

RESUMO

BACKGROUND: Depression has become one of the most common mood disorders in adolescents, with an increasing incidence each year. Abnormal activation of peripheral immunity causes an increase in pro-inflammatory factors, which in turn affects neuroendocrine dysfunction and alters neurobiochemistry, leading to depression. In this study, we aimed to explore the relationship between inflammatory immune function and intestinal flora in adolescents with first-episode depression. METHODS: A total of 170 cases of adolescent patients with first-episode depression who attended our hospital from January 2020 to March 2023 were retrospectively selected as the observation group. Simultaneously, 170 individuals who underwent a healthy physical examination during the same period were chosen as the control group. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), substance P (SP), neuropeptide Y (NPY), serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 in the patients. Flow cytometry was utilized to assess the levels of T-lymphocytes CD3+, CD4+, and CD8+ cells. The levels of 16S ribosomal RNA (16SrRNA) method were used to determine the intestinal flora of the subjects in both groups. Inflammatory factor levels, immune function, and intestinal flora expression were observed, and correlation analysis was performed. RESULTS: The levels of 5-HT and NPY in the observation group were lower than those in the control group. The SP level was significantly higher in the observation group compared to the control group (p < 0.05). The observation group demonstrated significantly higher TNF-α, IL-1ß, and IL-6 levels than the control group (p < 0.05). The values of CD3+, CD4+, CD4+/CD8+ in the observation group were lower than those in the control group (p < 0.05), whereas the CD8+ values were notably higher (p < 0.05). Bifidobacterium, Escherichia coli, Lactobacillus, and Bacteroides in the observation group were less than those in the control group (p < 0.05). The content of Bifidobacterium was negatively correlated with the level of TNF-α (r = -0.358, p < 0.001), positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = 0.490, 0.169, 0.165, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.154, p < 0.05). The level of Escherichia coli content was negatively correlated with the levels of IL-6, CD3+, CD4+, CD4+/CD8+ (r = -0.483, -0.548, -0.317, -0.328, p < 0.001), and positively correlated with the levels of CD8+ (r = 0.325, p < 0.001). The content of Lactobacillus was positively correlated with the levels of CD3+, CD4+, CD4+/CD8+ (r = 0.552, 0.188, 0.194, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.186, p < 0.05). The content of Bacteroides was positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = -0.570, -0.183, -0.193, p < 0.05), and negatively correlated with the level of CD8+ levels were positively correlated (r = 0.187, p < 0.05). CONCLUSIONS: The intestinal flora is related to the level of inflammatory factors and immune function. Further study on the relationship between intestinal flora, inflammatory immune function, and depression could offer novel insights for the prevention and treatment of depressive disorders.


Assuntos
Microbioma Gastrointestinal , Fator de Necrose Tumoral alfa , Humanos , Adolescente , Interleucina-6 , Depressão , Estudos Retrospectivos , Serotonina , Escherichia coli , Imunidade
5.
Adv Exp Med Biol ; 1444: 145-161, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467978

RESUMO

Inflammation is a complex process that protects our body from various insults such as infection, injury, and stress. Proper inflammation is beneficial to eliminate the insults and maintain organ homeostasis, however, it can become detrimental if uncontrolled. To tightly regulate inflammation, post-transcriptional mechanisms governing RNA metabolism play a crucial role in monitoring the expression of immune-related genes, such as tumor necrosis factor (TNF) and interleukin-6 (IL-6). These mechanisms involve the coordinated action of various RNA-binding proteins (RBPs), including the Regnase family, Roquin, and RNA methyltransferases, which are responsible for mRNA decay and/or translation regulation. The collaborative efforts of these RBPs are essential in preventing aberrant immune response activation and consequently safeguarding against inflammatory and autoimmune diseases. This review provides an overview of recent advancements in our understanding of post-transcriptional regulation within the immune system and explores the specific roles of individual RBPs in RNA metabolism and regulation.


Assuntos
Regulação da Expressão Gênica , Inflamação , Humanos , Inflamação/metabolismo , Imunidade/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RNA/genética
6.
Front Cell Infect Microbiol ; 14: 1342354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476165

RESUMO

Transplantation is the treatment of choice for several end-stage organ defects: it considerably improves patient survival and quality of life. However, post-transplant recipients may experience episodes of rejection that can favor or ultimately lead to graft loss. Graft maintenance requires a complex and life-long immunosuppressive treatment. Different immunosuppressive drugs (i.e., calcineurin inhibitors, glucocorticoids, biological immunosuppressive agents, mammalian target of rapamycin inhibitors, and antiproliferative or antimetabolic agents) are used in combination to mitigate the immune response against the allograft. Unfortunately, the use of these antirejection agents may lead to opportunistic infections, metabolic (e.g., post-transplant diabetes mellitus) or cardiovascular (e.g., arterial hypertension) disorders, cancer (e.g., non-Hodgkin lymphoma) and other adverse effects. Lately, immunosuppressive drugs have also been associated with gut microbiome alterations, known as dysbiosis, and were shown to affect gut microbiota-derived short-chain fatty acids (SCFA) production. SCFA play a key immunomodulatory role in physiological conditions, and their impairment in transplant patients could partly counterbalance the effect of immunosuppressive drugs leading to the activation of deleterious pathways and graft rejection. In this review, we will first present an overview of the mechanisms of graft rejection that are prevented by the immunosuppressive protocol. Next, we will explain the dynamic changes of the gut microbiota during transplantation, focusing on SCFA. Finally, we will describe the known functions of SCFA in regulating immune-inflammatory reactions and discuss the impact of SCFA impairment in immunosuppressive drug treated patients.


Assuntos
Microbioma Gastrointestinal , Transplante de Órgãos , Humanos , Qualidade de Vida , Imunossupressores , Imunidade
7.
Front Cell Infect Microbiol ; 14: 1296769, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476164

RESUMO

Intestinal parasitic infections caused by helminths are globally distributed and are a major cause of morbidity worldwide. Parasites may modulate the virulence, gut microbiota diversity and host responses during infection. Despite numerous works, little is known about the complex interaction between parasites and the gut microbiota. In the present study, the complex interplay between parasites and the gut microbiota was investigated. A total of 12 bacterial strains across four major families, including Enterobacteriaceae, Morganellaceae, Flavobacteriaceae, and Pseudomonadaceae, were isolated from Channa punctata, infected with the nematode species Aporcella sp., Axonchium sp., Tylencholaimus mirabilis, and Dioctophyme renale. The findings revealed that nematode infection shaped the fish gut bacterial microbiota and significantly affected their virulence levels. Nematode-infected fish bacterial isolates are more likely to be pathogenic, with elevated hemolytic activity and biofilm formation, causing high fish mortality. In contrast, isolates recovered further from non-parasitised C. punctata were observed to be non-pathogenic and had negligible hemolytic activity and biofilm formation. Antibiogram analysis of the bacterial isolates revealed a disproportionately high percentage of bacteria that were either marginally or multidrug resistant, suggesting that parasitic infection-induced stress modulates the gut microenvironment and enables colonization by antibiotic-resistant strains. This isolation-based study provides an avenue to unravel the influence of parasitic infection on gut bacterial characteristics, which is valuable for understanding the infection mechanism and designing further studies aimed at optimizing treatment strategies. In addition, the cultured isolates can supplement future gut microbiome studies by providing wet lab specimens to compare (meta)genomic information discovered within the gut microenvironment of fish.


Assuntos
Microbioma Gastrointestinal , Helmintos , Enteropatias Parasitárias , Nematoides , Parasitos , Humanos , Animais , Microbioma Gastrointestinal/fisiologia , Bactérias , Peixes , Imunidade
8.
PLoS One ; 19(3): e0297387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38470874

RESUMO

Head and neck cancer treatment often consists of surgical resection of the tumor followed by ionizing radiation (IR), which can damage surrounding tissues and cause adverse side effects. The underlying mechanisms of radiation-induced salivary gland dysfunction are not fully understood, and treatment options are scarce and ineffective. The wound healing process is a necessary response to tissue injury, and broadly consists of inflammatory, proliferative, and redifferentiation phases with immune cells playing key roles in all three phases. In this study, select immune cells were phenotyped and quantified, and certain cytokine and chemokine concentrations were measured in mouse parotid glands after IR. Further, we used a model where glandular function is restored to assess the immune phenotype in a regenerative response. These data suggest that irradiated parotid tissue does not progress through a typical inflammatory response observed in wounds that heal. Specifically, total immune cells (CD45+) decrease at days 2 and 5 following IR, macrophages (F4/80+CD11b+) decrease at day 2 and 5 and increase at day 30, while neutrophils (Ly6G+CD11b+) significantly increase at day 30 following IR. Additionally, radiation treatment reduces CD3- cells at all time points, significantly increases CD3+/CD4+CD8+ double positive cells, and significantly reduces CD3+/CD4-CD8- double negative cells at day 30 after IR. Previous data indicate that post-IR treatment with IGF-1 restores salivary gland function at day 30, and IGF-1 injections attenuate the increase in macrophages, neutrophils, and CD4+CD8+ T cells observed at day 30 following IR. Taken together, these data indicate that parotid salivary tissue exhibits a dysregulated immune response following radiation treatment which may contribute to chronic loss of function phenotype in head and neck cancer survivors.


Assuntos
Neoplasias de Cabeça e Pescoço , Glândula Parótida , Camundongos , Animais , Glândula Parótida/efeitos da radiação , Fator de Crescimento Insulin-Like I , Glândulas Salivares , Imunidade
9.
Nat Commun ; 15(1): 2274, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480702

RESUMO

One of the hopes for overcoming the antibiotic resistance crisis is the use of bacteriophages to combat bacterial infections, the so-called phage therapy. This therapeutic approach is generally believed to be safe for humans and animals as phages should infect only prokaryotic cells. Nevertheless, recent studies suggested that bacteriophages might be recognized by eukaryotic cells, inducing specific cellular responses. Here we show that in chickens infected with Salmonella enterica and treated with a phage cocktail, bacteriophages are initially recognized by animal cells as viruses, however, the cGAS-STING pathway (one of two major pathways of the innate antiviral response) is blocked at the stage of the IRF3 transcription factor phosphorylation. This inhibition is due to the inability of RNA polymerase III to recognize phage DNA and to produce dsRNA molecules which are necessary to stimulate a large protein complex indispensable for IRF3 phosphorylation, indicating the mechanism of the antiviral response impairment.


Assuntos
Bacteriófagos , Terapia por Fagos , Humanos , Animais , Bacteriófagos/fisiologia , Galinhas , Imunidade , Antivirais
10.
Front Immunol ; 15: 1328401, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481989

RESUMO

Background: Ascaris lumbricoides cystatin (Al-CPI) prevents the development of allergic airway inflammation and dextran-induced colitis in mice models. It has been suggested that helminth-derived cystatins inhibit cathepsins in dendritic cells (DC), but their immunomodulatory mechanisms are unclear. We aimed to analyze the transcriptional profile of human monocyte-derived DC (moDC) upon stimulation with Al-CPI to elucidate target genes and pathways of parasite immunomodulation. Methods: moDC were generated from peripheral blood monocytes from six healthy human donors of Denmark, stimulated with 1 µM of Al-CPI, and cultured for 5 hours at 37°C. RNA was sequenced using TrueSeq RNA libraries and the NextSeq 550 v2.5 (75 cycles) sequencing kit (Illumina, Inc). After QC, reads were aligned to the human GRCh38 genome using Spliced Transcripts Alignment to a Reference (STAR) software. Differential expression was calculated by DESEq2 and expressed in fold changes (FC). Cell surface markers and cytokine production by moDC were evaluated by flow cytometry. Results: Compared to unstimulated cells, Al-CPI stimulated moDC showed differential expression of 444 transcripts (|FC| ≥1.3). The top significant differences were in Kruppel-like factor 10 (KLF10, FC 3.3, PBH = 3 x 10-136), palladin (FC 2, PBH = 3 x 10-41), and the low-density lipoprotein receptor (LDLR, FC 2.6, PBH = 5 x 10-41). Upregulated genes were enriched in regulation of cholesterol biosynthesis by sterol regulatory element-binding proteins (SREBP) signaling pathways and immune pathways. Several genes in the cholesterol biosynthetic pathway showed significantly increased expression upon Al-CPI stimulation, even in the presence of lipopolysaccharide (LPS). Regarding the pathway of negative regulation of immune response, we found a significant decrease in the cell surface expression of CD86, HLA-DR, and PD-L1 upon stimulation with 1 µM Al-CPI. Conclusion: Al-CPI modifies the transcriptome of moDC, increasing several transcripts encoding enzymes involved in cholesterol biosynthesis and SREBP signaling. Moreover, Al-CPI target several transcripts in the TNF-alpha signaling pathway influencing cytokine release by moDC. In addition, mRNA levels of genes encoding KLF10 and other members of the TGF beta and the IL-10 families were also modified by Al-CPI stimulation. The regulation of the mevalonate pathway and cholesterol biosynthesis suggests new mechanisms involved in DC responses to helminth immunomodulatory molecules.


Assuntos
Cistatinas , Monócitos , Humanos , Animais , Camundongos , Ascaris lumbricoides , Ácido Mevalônico/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Diferenciação Celular , Citocinas/metabolismo , Inflamação/metabolismo , Imunidade , Células Dendríticas , RNA/metabolismo
11.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473845

RESUMO

The caspase recruitment domain-containing protein 9 (CARD9) is an intracellular adaptor protein that is abundantly expressed in cells of the myeloid lineage, such as neutrophils, macrophages, and dendritic cells. CARD9 plays a critical role in host immunity against infections caused by fungi, bacteria, and viruses. A CARD9 deficiency impairs the production of inflammatory cytokines and chemokines as well as migration and infiltration, thereby increasing susceptibility to infections. However, CARD9 signaling varies depending on the pathogen causing the infection. Furthermore, different studies have reported altered CARD9-mediated signaling even with the same pathogen. Therefore, this review focuses on and elucidates the current literature on varied CARD9 signaling in response to various infectious stimuli in humans and experimental mice models.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Citocinas , Humanos , Animais , Camundongos , Citocinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Imunidade , Transdução de Sinais , Macrófagos/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo
12.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474146

RESUMO

Immune alterations in end-stage renal patients receiving hemodialysis are complex and predispose patients to infections. Anticoagulation may also play an immunomodulatory role in addition to the accumulation of uremic toxins and the effects of the dialysis procedure. Accordingly, it has been recently shown that the infection rate increases in patients under regional citrate anticoagulation (RCA) compared with systemic heparin anticoagulation (SHA). We hypothesized that RCA affects the immune status of hemodialysis patients by targeting monocytes. In a cohort of 38 end-stage renal patients undergoing hemodialysis, we demonstrated that whole blood monocytes of patients receiving RCA-but not SHA-failed to upregulate surface activation markers, like human leukocyte antigen class II (HLA-DR), after stressful insults, indicating a state of deactivation during and immediately after dialysis. Additionally, RNA sequencing (RNA-seq) data and gene set enrichment analysis of pre-dialysis monocytes evidenced a great and complex difference between the groups given that, in the RCA group, monocytes displayed a dramatic transcriptional change with increased expression of genes related to the cell cycle regulation, cellular metabolism, and cytokine signaling, compatible with the reprogramming of the immune response. Transcriptomic changes in pre-dialysis monocytes signalize the lasting nature of the RCA-related effects, suggesting that monocytes are affected even beyond the dialysis session. Furthermore, these findings demonstrate that RCA-but not SHA-impairs the response of monocytes to activation stimuli and alters the immune status of these patients with potential clinical implications.


Assuntos
Anticoagulantes , Ácido Cítrico , Humanos , Ácido Cítrico/farmacologia , Anticoagulantes/farmacologia , Monócitos , Citratos , Heparina , Diálise Renal/métodos , Imunidade
13.
Exp Dermatol ; 33(3): e15021, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38429832

RESUMO

Langerhans cells (LCs) are mainly present in the epidermis and mucosa, and have important roles during skin infection. Migration of LCs to lymph nodes is essential for antigen presentation. However, due to the difficulties in isolating and culturing human LCs, it is not fully understood how LCs move and interact with the extracellular matrix (ECM) through their adhesion molecules such as integrin, during the immune responses. In this study, we aimed to investigate LC motility, cell shape and the role of integrin under inflammatory conditions using monocyte-derived Langerhans cells (moLCs) as a model. As a result, lipopolysaccharide (LPS) stimulation increased adhesion on fibronectin coated substrate and integrin α5 expression in moLCs. Time-lapse imaging of moLCs revealed that stimulation with LPS elongated cell shape, whilst decreasing their motility. Additionally, this decrease in motility was not observed when pre-treated with a neutralising antibody targeting integrin α5. Together, our data suggested that activation of LCs decreases their motility by promoting integrin α5 expression to enhance their affinity to the fibronectin, which may contribute to their migration during inflammation.


Assuntos
Integrina alfa5 , Células de Langerhans , Humanos , Fibronectinas/metabolismo , Imunidade , Integrina alfa5/metabolismo , Integrinas/metabolismo , Lipopolissacarídeos/farmacologia , Monócitos
14.
Zhonghua Yan Ke Za Zhi ; 60(3): 289-295, 2024 Mar 11.
Artigo em Chinês | MEDLINE | ID: mdl-38462380

RESUMO

Adeno-associated virus (AAV) vectors have been widely employed in gene therapy for ocular and systemic diseases. However, clinical trial outcomes have indicated that gene therapy may trigger severe adverse events associated with immune-inflammatory reactions, thereby impacting the safety and efficacy of gene therapy. The immune-inflammatory reaction induced after gene therapy in the eye is referred to as gene therapy-associated uveitis, which has become a major obstacle limiting the long-term and effective use of ocular gene therapy. This review comprehensively explores four aspects: the immune response mechanisms of gene therapy, ocular manifestations of associated uveitis, factors influencing immune inflammation, and preventive and therapeutic strategies. The aim is to provide insights for the development of safer and more effective ocular gene therapy.


Assuntos
Dependovirus , Uveíte , Humanos , Dependovirus/genética , Vetores Genéticos , Terapia Genética , Uveíte/terapia , Imunidade
15.
Parasite Immunol ; 46(3): e13029, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465509

RESUMO

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.


Assuntos
Esquistossomose Japônica , Esquistossomose , Humanos , Camundongos , Animais , Interleucina-4 , Cirrose Hepática , Esquistossomose/complicações , Fígado , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Imunidade
16.
Saudi Med J ; 45(3): 223-229, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38438201

RESUMO

Lung cancer is a complicated and challenging disease and is one of the most common causes of cancer-related mortality worldwide. Within the lung microenvironment, specific cytokines, including the B cell activation factor (BAFF) and the A proliferation-inducing ligand (APRIL), are produce by various cells, notably airway epithelial cells, in response allergic inflammation or pulmonary infection. These cytokines play a critical role in maintaining local immune responses and fostering the survival of immune cells. The BAFF and APRIL system have been connected in a range of malignancies and have shown their potential in inducing drug resistance and promoting cancer progression. This review highlights recent studies on the involvement of BAFF and APRIL in various cancers, focusing mainly on their role in lung cancer, and discusses the possibility of these molecules in contributing to drug resistance and cancer progression following pulmonary infection. We suggest consideration the targeting BAFF and APRIL or their respective receptors as promising novel therapies for effective treatment of lung cancer, especially post pulmonary infection. However, it remains important to conduct further investigations to fully elucidate the precise mechanisms underlying how the BAFF and APRIL systems enhance cancer survival and drug resistance subsequent pulmonary infections.


Assuntos
Neoplasias Pulmonares , Pneumonia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Ligantes , Citocinas , Imunidade , Microambiente Tumoral
17.
Front Immunol ; 15: 1298749, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440733

RESUMO

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.


Assuntos
Hansenostáticos , Hanseníase , Humanos , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/genética , Hanseníase/prevenção & controle , Rifampina , Imunidade
19.
Mol Biol Rep ; 51(1): 408, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460043

RESUMO

BACKGROUND: To describe an oncolytic adenovirus (OAd) encoding SP-SA-E7-4-1BBL that is capable of inducing tumor regression in therapeutic assays. Herein, we tested whether the antitumor effect is given by the induction of a tumor-specific immune response, as well as the minimum dose needed to elicit antitumor protection and monitor the OAd biodistribution over time. METHODS AND RESULTS: C57BL/6 mice (n = 5) per group were immunized twice with OAds encoding SP-SA-E7-4-1BBL, SA-E7-4-1BBL, or SP-SA-4-1BBL and challenged with TC-1 cancer cells. The DNA construct SP-SA-E7-4-1BBL was employed as a control via biolistic or PBS injection. Groups without tumor development at 47 days were rechallenged with TC-1 cells, and follow-up lasted until day 90. The minimum dose of OAd to induce the antitumor effect was established by immunization using serial dilution doses. The cytometry bead assay and the ELISpot assay were used to evaluate cytokine release in response to ex vivo antigenic stimulation. The distribution profile of the OAd vaccine was evaluated in the different organs by histological, immunohistochemical and qPCR analyses. The OAd SP-SA-E7-4-1BBL-immunized mice did not develop tumors even in a rechallenge. A protective antitumor effect was observed from a dose that is one hundredth of most reports of adenoviral vaccines. Immunization with OAd increases Interferon-gamma-producing cells in response to antigen stimulation. OAd was detected in tumors over time, with significant morphological changes, contrary to nontumor tissues. CONCLUSIONS: The OAd SP-SA-E7-4-1BBL vaccine confers a prophylactic, safe, long-lasting, and antigen-dependent antitumor effect mediated by a Th1 antitumor immune response.


Assuntos
Vacinas Anticâncer , Neoplasias , Animais , Camundongos , Papillomavirus Humano 16 , Ligante 4-1BB/genética , Ligante 4-1BB/farmacologia , Distribuição Tecidual , Camundongos Endogâmicos C57BL , Adenoviridae/genética , Imunidade , Neoplasias/terapia
20.
Aging Dis ; 15(2): 787-803, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447216

RESUMO

Cellular senescence is an irreversible and multifaceted process inducing tissue dysfunction and organismal aging, and thus the clearance of senescent cells can prevent or delay the onset of aging-related pathologies. Herein, we developed an augmented photothermal therapy strategy integrated with an antibody against ß2-microglobulin (aB2MG) and an immune adjuvant imiquimod (R837) to effectively accelerate senescent cell apoptosis and clearance under a near-infrared light. With this strategy, the designed CroR@aB2MG enables the targeting of senescent cells and the application of photothermal therapy concomitantly, the initiation of immune clearance subsequently, and finally the realization of protective effects against senescence. Our results showed that the photo-induced heating effect caused senescent cells to quickly undergo apoptosis and the synchronous immune response accelerated the clearance of senescent cells in vitro and in vivo. Therefore, this photoactivated speedy clearing strategy may provide an efficient way for the treatment of senescence-related diseases by eliminating senescent cells with biomaterials.


Assuntos
Anticorpos , Terapia Fototérmica , Senescência Celular , Imunidade
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