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1.
Int J Med Sci ; 18(16): 3788-3793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790054

RESUMO

As the world is racing to develop perpetual immunity to the SARS-CoV-2 virus. The emergence of new viral strains, together with vaccination and reinfections, are all contributing to a long-term immunity against the deadly virus that has taken over the world since its introduction to humans in late December 2019. The discovery that more than 95 percent of people who recovered from COVID-19 had long-lasting immunity and that asymptomatic people have a different immune response to SARS-CoV-2 than symptomatic people has shifted attention to how our immune system initiates such diverse responses. These findings have provided reason to believe that SARS-CoV-2 days are numbered. Hundreds of research papers have been published on the causes of long-lasting immune responses and variations in the numbers of different immune cell types in COVID 19 survivors, but the main reason of these differences has still not been adequately identified. In this article, we focus on the activation-induced cytidine deaminase (AID), which initiates molecular processes that allow our immune system to generate antibodies against SARS-CoV-2. To establish lasting immunity to SARS-CoV-2, we suggest that AID could be the key to unlocking it.


Assuntos
COVID-19/imunologia , Citidina Desaminase/genética , Imunidade/genética , SARS-CoV-2/imunologia , COVID-19/virologia , Citidina/genética , Citidina/imunologia , Citidina Desaminase/imunologia , Desaminação/imunologia , Humanos , SARS-CoV-2/patogenicidade , Vacinação
2.
Nat Commun ; 12(1): 6277, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725327

RESUMO

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Vetores Genéticos , Imunidade , Adenoviridae , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Cricetinae , Citocinas , Feminino , Imunização , Imunização Secundária , Masculino , Vacina contra Sarampo/imunologia , Mesocricetus , Camundongos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
3.
Cell ; 184(23): 5699-5714.e11, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34735795

RESUMO

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.


Assuntos
Vacinas contra COVID-19/imunologia , Vacinas Sintéticas/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Apresentação Cruzada/imunologia , Relação Dose-Resposta Imunológica , Grupos Étnicos , Feminino , Humanos , Imunidade , Imunoglobulina G/imunologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Padrões de Referência , SARS-CoV-2/imunologia , Linfócitos T/imunologia , Resultado do Tratamento , Adulto Jovem
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(10): 1492-1500, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34755664

RESUMO

OBJECTIVE: To investigate the characteristics of immune cell subsets in the lung tissues of patients with chronic obstructive pulmonary disease (COPD) and the mechanism of Liuwei Buqi capsule in modulating immune and inflammatory imbalance in COPD. METHODS: We downloaded COPD-related single-cell RNA sequencing data from Gene Expression Omnibus (GEO) and identified COPD immune cell subsets using the Seurat package in the R software to construct an immune cell subsets-differential genes network. The target genes and active ingredients of Liuwei Buqi capsule were obtained from the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the Liuwei Buqi capsule-immune cell subsets-target genes network was constructed by mapping the target genes to the differentially expressed genes in each immune cell subset. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to analyze significantly enriched pathways of the target genes, and the key genes involved in the top 20 pathways were identified. In a rat model of COPD, we investigated the effects of Liuwei Buqi capsule on pulmonary function, lung tissue pathology, serum levels of IL-1ß, NF-κB, and TNF-α, and expressions of IKBα, JNK, c-JUN, and c-FOS proteins in the lung tissue. RESULTS: A total of 18 immune-related cell subsets, including macrophages and alveolar macrophages, were identified in both COPD patients and healthy control subjects, and the patients with COPD showed significant changes the percentages of macrophages, cDC1, pDC, mast cells, T cells, and mature dendritic cells (P < 0.05). Liuwei Buqi capsules targeted multiple immune cell subsets, and the identified target genes were enriched mostly in such immune and inflammation-related signaling pathways as lipids and atherosclerosis, IL-17 signaling pathway, Toll-like receptor signaling pathway, and TNF signaling pathway; the genes CXCL8, IL1B, JUN, NFKBIA, MAPK8, and FOS were the key genes involved in the significantly enriched pathways. In the rat models of COPD, treatment with Liuwei Buqi capsule significantly improved pulmonary function, alleviated lung pathologies, reduced serum levels of IL-1ß, TNF-α, and NF-κB (P < 0.05) and pulmonary expressions of JNK, c-JUN, and c-FOS (P < 0.01) protein, and increased pulmonary expression of IκBα (P < 0.01). CONCLUSION: Liuwei Buqi capsule may play an immunomodulatory role by targeting multiple immune cell subsets in the lung tissue of COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Imunidade , Pulmão/metabolismo , NF-kappa B/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Transdução de Sinais
5.
Phytomedicine ; 93: 153811, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34735908

RESUMO

BACKGROUND: The immune-enhancing effects of red Platycodon grandiflorus root extract (RPGE) has been reported in vitro and in vivo, but there are few studies on humans. Therefore, this study aimed to investigate the efficacy and safety of RPGE in enhancing immune function in healthy subjects. SUBJECTS AND METHODS: An 8-week randomized, double-blind, parallel, placebo-controlled clinical trial was conducted at the Gachon University Gil Medical Center, Incheon, South Korea. A total of 100 adults aged 20-75 years with white blood cell counts of 3000-10,000 cell/µL were randomly divided into two groups (RPGE group, 50 and placebo group, 50) using a computer-generated random list with a 1:1 allocation ratio. The subjects consumed RPGE (2 times/day, 2 tablets/time, 375 mg RPGE powder/tablet) or placebo for 8 weeks. All test foods for the human study were coded and administered under double-blind conditions. The primary outcome was a change in the NK cell activity after 8 weeks of treatment compared to the baseline. RESULTS: Among 100 subjects enrolled for the study, 87 completed the study. NK cell activity (p = 0.005) and IFN-γ level (p = 0.003) of the RPGE group (n = 41) were higher than those of the placebo group (n = 46). The findings of the safety assessment revealed absence of clinically significant changes in any test and serious adverse events throughout the study. CONCLUSION: In conclusion, these results demonstrate the efficacy and safety of RPGE, suggesting it to be a beneficial agent for enhancing immune function in humans. TRIAL REGISTRATION: CRIS Registration Number KCT0005945, https://cris.nih.go.kr.


Assuntos
Platycodon , Método Duplo-Cego , Humanos , Imunidade , Extratos Vegetais/farmacologia , República da Coreia , Resultado do Tratamento
6.
World J Gastroenterol ; 27(40): 6775-6793, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34790007

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with high lethality. Even with surgery, radiotherapy, chemotherapy, and other locoregional or systemic therapies, the survival rates for PDAC are low and have not significantly changed in the past decades. The special characteristics of the PDAC's microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease. PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells. The pancreatic microenvironment is a fibrotic, microvascularized stroma that isolates the tumor from systemic vascularization. Immunotherapy, a novel approach that has demonstrated effectiveness in certain solid tumors, has failed to show any practice-changing results in pancreatic cancer, with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden, which show prolonged survival rates with immunotherapy. Currently, numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, alone or in combination with other immunotherapeutic agents, chemoradiotherapy, and other targeted therapies. A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/terapia , Humanos , Imunidade , Imunoterapia , Neoplasias Pancreáticas/terapia , Microambiente Tumoral
7.
Front Immunol ; 12: 765965, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721437

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome's potential as a biomarker and therapeutic target.


Assuntos
COVID-19/microbiologia , Síndrome da Liberação de Citocina/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , SARS-CoV-2/fisiologia , COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Disbiose/imunologia , Humanos , Imunidade , Inflamação
8.
Front Immunol ; 12: 732913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737743

RESUMO

Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the viral infection that develops into a severe course of COVID-19. Moreover, sequela studies of individuals 6 months after having COVID-19 show a higher risk of metabolic comorbidities including obesity, diabetes, and kidney disease. These collectively implicate an inter-systemic dimension to understanding the association between obesity and COVID-19 and suggest an interdisciplinary intervention for relief of obesity-COVID-19 complications beyond the phase of acute infection.


Assuntos
COVID-19/imunologia , COVID-19/metabolismo , Obesidade/imunologia , Obesidade/metabolismo , COVID-19/complicações , Progressão da Doença , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade , Doenças Metabólicas/imunologia , Doenças Metabólicas/metabolismo , Obesidade/complicações , Prognóstico , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
9.
Front Cell Infect Microbiol ; 11: 753249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760721

RESUMO

Background: Novel coronavirus SARS-CoV2 is evolving continuously with emergence of several variants of increasing transmission capabilities and pandemic potential. Generation of variants occurs through accumulation of mutations due to the RNA nature of viral genome, which is further enhanced by variable selection pressures of this ongoing pandemic. COVID-19 presentations of SARS-CoV2 are mainly pulmonary manifestations with or without mild gastrointestinal (GI) and hepatic symptoms. However, the virus has evolved beyond pulmonary manifestations to multisystem disorder due to systemic inflammation and cytokine storm. Definitive cause of acute or late onset of inflammation, infection in various organs, and host response to emerging variants lacks clarity and needs elucidation. Several studies have reported underlying diseases including diabetes, hypertension, obesity, cardio- and cerebrovascular disorders, and immunocompromised conditions as significant risk factors for severe form of COVID-19. Pre-existing liver and GI diseases are also highly predominant in the population, which can alter COVID-19 outcome due to altered immune status and host response. We aim to review the emerging variants of SARS-CoV2 and host response in patients with pre-existing liver and GI diseases. Methods: In this review, we have elucidated the emergence and characteristic features of new SARS-CoV2 variants, mechanisms of infection and host immune response, GI and hepatic manifestation with radiologic features of COVID-19, and outcomes in pre-existing liver and GI diseases. Key Findings: Emerging variants of concern (VOC) have shown increased transmissibility and virulence with severe COVID-19 presentation and mortality. There is a drastic swift of variants from the first wave to the next wave of infections with predominated major VOC including alpha (B.1.1.7, UK), beta (B.1.351, South Africa), gamma (B.1.1.28.1, Brazil), and delta (B1.1.617, India) variants. The mutations in the spike protein of VOC are implicated for increased receptor binding (N501Y, P681R) and immune escape (L452R, E484K/Q, T478K/R) to host response. Pre-existing liver and GI diseases not only have altered tissue expression and distribution of viral entry ACE2 receptor but also host protease TMPRSS2, which is required for both spike protein binding and cleavage to initiate infection. Altered immune status due to pre-existing conditions results in delayed virus clearance or prolonged viremia. Even though GI and hepatic manifestations of SARS-CoV2 are less severe, the detection of virus in patient's stool indicates GI tropism, replication, and shedding from the GI tract. COVID-19-induced liver injury, acute hepatic decompensation, and incidences of acute-on-chronic liver failure may change the disease outcomes. Conclusions: The changes in the spike protein of emerging variants, immunomodulation by viral proteins, and altered expression of host viral entry receptor in pre-existing diseases are the key determinants of host response to SARS-CoV2 and its disease outcome.


Assuntos
COVID-19 , Gastroenteropatias , Humanos , Imunidade , Fígado , RNA Viral , SARS-CoV-2
10.
BMC Infect Dis ; 21(1): 1029, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598701

RESUMO

BACKGROUND: To date, whether the immune response for SARS-CoV-2 infection among people living with HIV(PLWH) is different from HIV-naïve individuals is still not clear. METHODS: In this cohort study, COVID-19 patients admitted to hospitals in Wuhan between January 15 and April 1, 2020, were enrolled. Patients were categorized into PLWH and HIV-naïve group. All patients were followed up regularly (every 15 days) until November 30, 2020, and the immune response towards SARS-CoV-2 was observed. RESULTS: Totally, 18 PLWH and 185 HIV-naïve individuals with COVID-19 were enrolled. The positive conversion rates of IgG were 56% in PLWH and 88% in HIV-naïve patients respectively, and the peak was on the 45th day after COVID-19 onset. However, the positive rate of IgG dropped to 12% in PLWH and 33% among HIV-naïve individuals by the end of the study. The positive conversion rate of IgG among asymptomatic carriers is significantly lower than that among patients with moderate disease (AOR = 0.24, 95% CI 0.07-0.85). PLWH had a lower IgG seroconversion rate (AOR = 0.11, 95% CI 0.03-0.39) and shorter IgG duration (AHR = 3.99, 95% CI 1.43-11.13) compared to HIV-naïve individuals. Patients with higher lymphocyte counts at onset had a lower positive conversion rate (AOR = 0.30, 95% CI 0.10-0.87) and shorter duration for IgG (AHR = 4.01, 95% CI 1.78-9.02). CONCLUSIONS: The positive conversion rate of IgG for SARS-CoV-2 was relatively lower and quickly lost in PLWH.


Assuntos
COVID-19 , Infecções por HIV , Estudos de Coortes , Infecções por HIV/epidemiologia , Humanos , Imunidade , SARS-CoV-2
11.
World J Surg Oncol ; 19(1): 307, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34666774

RESUMO

BACKGROUND: To evaluate the immune function of gastric cancer patients after single-incision laparoscopic distal gastrectomy (SIDG) or multiport laparoscopic distal gastrectomy (MLDG) guided by enhanced recovery after surgery (ERAS). METHODS: A retrospective cohort study was performed on 120 patients who underwent laparoscopic distal gastrectomy for gastric cancer. The patients were divided into two groups according to operation method: group A (MLDG) and group B (SIDG), both guided by ERAS concept. The indicators reflecting immune function and inflammation, such as CD3+, CD4+, CD8+ and NK cell count, CD4+/CD8+ cell ratios, IgA, IgM and IgG levels, C-reactive protein (CRP), total lymphocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) were tested 3 days and 7 days after surgery. RESULTS: The skin incision length of patients in group B was significantly shorter than that in group A, but the operation time was significantly longer in group B than that in group A (P < 0.05). There were no significant differences in preoperative CD3+, CD4+, CD8+, natural killer (NK) cells, CD4+/CD8+, IgA, IgM and IgG levels between two groups (P < 0.05). Three days after surgery, the immune function indices were decreased in both groups, but with no significant difference between two groups (P > 0.05). On the 7th day after surgery, the immune indexes of both groups recovered somewhat, approaching the preoperative level (P > 0.05). Inflammation indexes increased 3 days after surgery and decreased 7 days after surgery in both groups, among them the CRP level in group A was higher than that in group B (P < 0.05). The 3-year survival rate were 96.7% in group A and 91.7% in group B, respectively, with no statistically significant difference. CONCLUSION: Compared with MLDG guided by ERAS, SIDG under the guidance of the ERAS concept has better cosmetic effect and similar effect on immune function of gastric cancer patients.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Neoplasias Gástricas , Gastrectomia , Humanos , Imunidade , Tempo de Internação , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
12.
BMC Genomics ; 22(1): 749, 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34657595

RESUMO

BACKGROUND: Bovine milk contains extracellular vesicles (EVs) that play a role in cellular communication, acting in either an autocrine, paracrine, or an exocrine manner. The unique properties of the EVs protect the cargo against degradation. We profiled the ncRNAs (non-coding RNA) present in the EVs from seven dairy products - raw whole milk, heat-treated skim milk, homogenized heat-treated skim milk, pasteurized homogenized skim milk, pasteurized heavy whipping cream, sweet cream buttermilk and cultured buttermilk with four replicates each, obtained at different processing steps from a commercial dairy plant. EVs and their cargo were extracted by using a validated commercial kit that has been shown to be efficient and specific for EVs. Further, to find the annotation of ncRNAs, we probed bovine and other organism repositories(such as miRBase, miRTarBase, Ensemble) to find homolog ncRNA annotation in case the annotations of ncRNA are not available in Bos Taurus database. RESULTS: Specifically, 30 microRNAs (miRNAs), were isolated throughout all the seven milk samples, which later when annotated with their corresponding 1546 putative gene targets have functions associated with immune response and growth and development. This indicates the potential for these ncRNAs to beneficially support mammary health and growth for the cow as well as neonatal gut maturation. The most abundant miRNAs were bta-miR-125a and human homolog miR-718 based on the abundance values of read count obtained from the milk samples.bta-miR-125a is involved in host bacterial and viral immune response, and human homolog miR-718 is involved in the regulation of p53, VEGF, and IGF signaling pathways, respectively. Sixty-two miRNAs were up-regulated and 121 miRNAs were down-regulated throughout all the milk samples when compared to raw whole milk. In addition, our study explored the putative roles of other ncRNAs which included 88 piRNAs (piwi-interacting RNA), 64 antisense RNAs, and 105 lincRNAs (long-intergenic ncRNAs) contained in the bovine exosomes. CONCLUSION: Together, the results indicate that bovine milk contains significant numbers of ncRNAs with putative regulatory targets associated with immune- and developmental-functions important for neonatal bovine health, and that processing significantly affects the ncRNA expression values; but statistical testing of overall abundance(read counts) of all miRNA samples suggests abundance values aren't much affected. This can be attributed to the breakage of exosomal vesicles during the processing stages. It is worth noting, however, that these gene regulatory targets are putative, and further evidence could be generated through experimental validation.


Assuntos
Exossomos , Vesículas Extracelulares , MicroRNAs , Leite/química , Animais , Bovinos , Feminino , Imunidade , MicroRNAs/genética , RNA não Traduzido/genética
13.
Nat Commun ; 12(1): 5857, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615877

RESUMO

The recently identified G-protein-coupled receptor GPR171 and its ligand BigLEN are thought to regulate food uptake and anxiety. Though GPR171 is commonly used as a T cell signature gene in transcriptomic studies, its potential role in T cell immunity has not been explored. Here we show that GPR171 is transcribed in T cells and its protein expression is induced upon antigen stimulation. The neuropeptide ligand BigLEN interacts with GPR171 to suppress T cell receptor-mediated signalling pathways and to inhibit T cell proliferation. Loss of GPR171 in T cells leads to hyperactivity to antigen stimulation and GPR171 knockout mice exhibit enhanced antitumor immunity. Blockade of GPR171 signalling by an antagonist promotes antitumor T cell immunity and improves immune checkpoint blockade therapies. Together, our study identifies the GPR171/BigLEN axis as a T cell checkpoint pathway that can be modulated for cancer immunotherapy.


Assuntos
Imunidade , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Linfócitos T/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Células HEK293 , Humanos , Imunoterapia , Ligantes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias/terapia , Neuropeptídeos/metabolismo , Receptores Acoplados a Proteínas G/deficiência , Transdução de Sinais
14.
BMC Genomics ; 22(1): 770, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34706639

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in several immune processes, including the immune response to vaccination, but most of them remain uncharacterised in livestock species. The mechanism of action of aluminium adjuvants as vaccine components is neither not fully understood. RESULTS: We built a transcriptome from sheep PBMCs RNA-seq data in order to identify unannotated lncRNAs and analysed their expression patterns along protein coding genes. We found 2284 novel lncRNAs and assessed their conservation in terms of sequence and synteny. Differential expression analysis performed between animals inoculated with commercial vaccines or aluminium adjuvant alone and the co-expression analysis revealed lncRNAs related to the immune response to vaccines and adjuvants. A group of co-expressed genes enriched in cytokine signalling and production highlighted the differences between different treatments. A number of differentially expressed lncRNAs were correlated with a divergently located protein-coding gene, such as the OSM cytokine. Other lncRNAs were predicted to act as sponges of miRNAs involved in immune response regulation. CONCLUSIONS: This work enlarges the lncRNA catalogue in sheep and puts an accent on their involvement in the immune response to repetitive vaccination, providing a basis for further characterisation of the non-coding sheep transcriptome within different immune cells.


Assuntos
RNA Longo não Codificante , Vacinas , Alumínio , Animais , Perfilação da Expressão Gênica , Imunidade/genética , RNA Longo não Codificante/genética , Ovinos , Transcriptoma
15.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639014

RESUMO

The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients' quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.


Assuntos
Antineoplásicos/efeitos adversos , Imunidade/efeitos dos fármacos , Imunidade/efeitos da radiação , Neoplasias/complicações , Neoplasias/imunologia , Radiação Ionizante , Radioterapia/efeitos adversos , Animais , Antineoplásicos/uso terapêutico , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Humanos , Modelos Animais , Neoplasias/terapia , Lesões por Radiação/etiologia , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Radioterapia/métodos
17.
Sci Transl Med ; 13(617): eabm2070, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34664978

RESUMO

[Figure: see text].


Assuntos
COVID-19 , SARS-CoV-2 , Feminino , Humanos , Imunidade , Gravidez
18.
Artigo em Inglês | MEDLINE | ID: mdl-34682706

RESUMO

Morganella morganii is one of the main etiological agents of hospital-acquired infections and no licensed vaccine is available against the pathogen. Herein, we designed a multi-epitope-based vaccine against M. morganii. Predicted proteins from fully sequenced genomes of the pathogen were subjected to a core sequences analysis, followed by the prioritization of non-redundant, host non-homologous and extracellular, outer membrane and periplasmic membrane virulent proteins as vaccine targets. Five proteins (TonB-dependent siderophore receptor, serralysin family metalloprotease, type 1 fimbrial protein, flagellar hook protein (FlgE), and pilus periplasmic chaperone) were shortlisted for the epitope prediction. The predicted epitopes were checked for antigenicity, toxicity, solubility, and binding affinity with the DRB*0101 allele. The selected epitopes were linked with each other through GPGPG linkers and were joined with the cholera toxin B subunit (CTBS) to boost immune responses. The tertiary structure of the vaccine was modeled and blindly docked with MHC-I, MHC-II, and Toll-like receptors 4 (TLR4). Molecular dynamic simulations of 250 nanoseconds affirmed that the designed vaccine showed stable conformation with the receptors. Further, intermolecular binding free energies demonstrated the domination of both the van der Waals and electrostatic energies. Overall, the results of the current study might help experimentalists to develop a novel vaccine against M. morganii.


Assuntos
Morganella morganii , Vacinas , Biologia Computacional , Epitopos de Linfócito T , Imunidade , Simulação de Acoplamento Molecular , Morganella morganii/genética
19.
Nat Commun ; 12(1): 5773, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599159

RESUMO

Protein localisation and translocation between intracellular compartments underlie almost all physiological processes. The hyperLOPIT proteomics platform combines mass spectrometry with state-of-the-art machine learning to map the subcellular location of thousands of proteins simultaneously. We combine global proteome analysis with hyperLOPIT in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during a lipopolysaccharide (LPS)-induced inflammatory response. We report a highly dynamic proteome in terms of both protein abundance and subcellular localisation, with alterations in the interferon response, endo-lysosomal system, plasma membrane reorganisation and cell migration. Proteins not previously associated with an LPS response were found to relocalise upon stimulation, the functional consequences of which are still unclear. By quantifying proteome-wide uncertainty through Bayesian modelling, a necessary role for protein relocalisation and the importance of taking a holistic overview of the LPS-driven immune response has been revealed. The data are showcased as an interactive application freely available for the scientific community.


Assuntos
Inflamação/metabolismo , Leucemia/metabolismo , Leucemia/patologia , Lipopolissacarídeos/farmacologia , Proteômica , Algoritmos , Anti-Infecciosos/metabolismo , Anti-Inflamatórios/metabolismo , Apresentação do Antígeno , Autofagossomos/metabolismo , Teorema de Bayes , Pontos de Checagem do Ciclo Celular , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Forma Celular , Humanos , Imunidade , Inflamação/patologia , Leucemia/imunologia , Ativação Linfocitária/imunologia , Lisossomos/metabolismo , Proteínas de Neoplasias/metabolismo , Transporte Proteico , Proteoma/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Células THP-1 , Fatores de Tempo , Vesículas Transportadoras/metabolismo , Regulação para Cima , Proteínas rho de Ligação ao GTP/metabolismo
20.
Nat Commun ; 12(1): 5819, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611155

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The continued spread of SARS-CoV-2 increases the probability of influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine the disease outcome of influenza A virus (IAV) and SARS-CoV-2 coinfection in K18-hACE2 mice. Our data indicate enhance susceptibility of IAV-infected mice to developing severe disease upon coinfection with SARS-CoV-2 two days later. In contrast to nonfatal influenza and lower mortality rates due to SARS-CoV-2 alone, this coinfection results in severe morbidity and nearly complete mortality. Coinfection is associated with elevated influenza viral loads in respiratory organs. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevents severe disease and mortality. This protection is antibody-dependent. These data experimentally support the necessity of seasonal influenza vaccination for reducing the risk of severe influenza/COVID-19 comorbidity during the COVID-19 pandemic.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Coinfecção/imunologia , Coinfecção/virologia , Imunidade , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Antivirais/imunologia , COVID-19/patologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/genética , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Regulação para Cima/genética , Carga Viral/imunologia
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