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1.
PLoS Negl Trop Dis ; 17(1): e0011020, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36634044

RESUMO

Extensive research has examined why some people have frequent Plasmodium falciparum malaria episodes in sub-Saharan Africa while others remain free of disease most of the time. In contrast, malaria risk heterogeneity remains little studied in regions where P. vivax is the dominant species. Are repeatedly infected people in vivax malaria settings such as the Amazon just unlucky? Here, we briefly review evidence that human genetic polymorphism and acquired immunity after repeated exposure to parasites can modulate the risk of P. vivax infection and disease in predictable ways. One-fifth of the hosts account for 80% or more of the community-wide vivax malaria burden and contribute disproportionally to onward transmission, representing a priority target of more intensive interventions to achieve malaria elimination. Importantly, high-risk individuals eventually develop clinical immunity, even in areas with very low or residual malaria transmission, and may constitute a large but silent parasite reservoir.


Assuntos
Malária Vivax , Humanos , Malária Vivax/genética , Malária Vivax/imunologia , Plasmodium vivax , Prevalência , Recidiva
2.
Nat Commun ; 14(1): 188, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635274

RESUMO

Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.


Assuntos
COVID-19 , Infecções por HIV , Tuberculose , Adulto , Humanos , África/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/imunologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , HIV-1 , Imunidade , SARS-CoV-2 , Tuberculose/complicações , Tuberculose/epidemiologia
3.
BJS Open ; 7(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36655328

RESUMO

BACKGROUND: Low-density granulocytes (LDGs) have been shown to be increased in the peripheral blood of patients with inflammatory and malignant diseases. This study evaluated LDGs in patients who underwent radical surgery for colorectal cancer (CRC) and their impact on survival. METHODS: Patients who underwent radical colectomy between 2017 to 2021 were screened for enrolment in the study. Peripheral blood was obtained in the operating room before and after surgery and cells were recovered from the mononuclear layer after density gradient preparations. The ratio of CD66b(+) LDG to CD45(+) leukocytes was determined with flow cytometry, and the association of the ratios with patient outcomes was examined. The main outcome of interest was recurrence-free survival (RFS). RESULTS: Out of 228 patients treated, 176 were enrolled, including 108 colonic and 68 rectal cancers. Overall, 38 patients were stage I, 30 were stage II, 72 were stage 3, and 36 were stage IV. The number of LDGs was markedly increased immediately after surgery and the proportion of LDGs correlated positively with operating time (r = 0.2806, P < 0.001) and intraoperative blood loss (r = 0.1838, P = 0.014). Purified LDGs produced high amounts of neutrophil extracellular traps after short-term culture and efficiently trapped tumour cells in vitro. The proportion of postoperative LDGs was significantly higher in 13 patients who developed recurrence (median 9 (range 1.63-47.0)) per cent versus median 2.93 ((range 0.035-59.45) per cent, P = 0.013). When cut-off values were set at 4.9 per cent, a higher proportion of LDGs was strongly and independently associated with decreased RFS (P = 0.005). In patients with stage III disease, adjuvant chemotherapy significantly improved RFS of patients with high ratios of LDGs, but not low LDGs. CONCLUSION: LDGs are recruited to circulating blood by surgical stress early in the postoperative interval after colectomy for colonic cancer and their postoperative proportion is correlated with recurrence.


Assuntos
Neoplasias Colorretais , Granulócitos , Humanos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Citometria de Fluxo , Granulócitos/imunologia , Granulócitos/patologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(1): 5-10, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36655657

RESUMO

OBJECTIVES: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. METHODS: A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome. RESULTS: Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P<0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination (P<0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group (P<0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer (P<0.05). CONCLUSIONS: Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.


Assuntos
COVID-19 , Ácidos Nucleicos , Criança , Humanos , Infecções Assintomáticas , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19 , Fibrinogênio , Interleucina-6 , Estudos Retrospectivos , SARS-CoV-2
5.
Nat Commun ; 14(1): 311, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658148

RESUMO

Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated a panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural infection and vaccination and showed that they recognize an immunogenic patch on the internal surface of the core RBD, which faces inwards and is hidden in the "down" state. These antibodies broadly neutralize wild type (Wuhan-Hu-1) SARS-CoV-2, Beta and Delta variants and some are effective against other sarbecoviruses. We observed a continuum of partially overlapping antibody epitopes from lower to upper part of the inner face of the RBD and some antibodies extend towards the receptor-binding motif. The majority of antibodies are substantially compromised by three mutational hotspots (S371L/F, S373P and S375F) in the lower part of the Omicron BA.1, BA.2 and BA.4/5 RBD. By contrast, antibody IY-2A induces a partial unfolding of this variable region and interacts with a conserved conformational epitope to tolerate all antigenic variations and neutralize diverse sarbecoviruses as well. This finding establishes that antibody recognition is not limited to the normal surface structures on the RBD. In conclusion, the delineation of functionally and structurally conserved RBD epitopes highlights potential vaccine and therapeutic candidates for COVID-19.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Epitopos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
6.
Arch Virol ; 168(2): 70, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36658439

RESUMO

Zika virus (ZIKV) is an arbovirus that was responsible for multiple outbreaks from 2007 to 2015. It has been linked to cases of microcephaly in Brazil in 2015, among other neurological disorders. Differences among strains might be the reason for different clinical outcomes of infection. To evaluate this hypothesis, we performed a comparative proteomic analysis of Vero cells infected with the African strain MR766 (ZIKVAFR) and the Brazilian strain 17 SM (ZIKVBR). A total of 550 proteins were identified as differentially expressed in ZIKVAFR- or ZIKVBR-infected cells compared to the control. The main findings included upregulation of immune system pathways (neutrophil degranulation and adaptive/innate immune system) and potential activation of immune-system-related pathways by ZIKVAFR (mTOR, JAK-STAT, NF-κB, and others) compared with the ZIKVBR/control. In addition, phagocytosis by macrophages and engulfment of leukocytes were activated in ZIKVAFR infection. An in vivo analysis using an immunocompetent C57BL/6N mouse model identified interstitial pneumonia with neutrophil infiltration in the lungs only in mice infected with ZIKVBR at 48 hours postinfection, with a significant amount of virus detected. Likewise, only animals infected with ZIKVBR had viral material in the cytoplasm of lung macrophages. These results suggest that activation of the immune system by ZIKVAFR infection may lead to faster viral clearance by immune cells.


Assuntos
Evasão da Resposta Imune , Infecção por Zika virus , Zika virus , Animais , Camundongos , Brasil , Chlorocebus aethiops , Camundongos Endogâmicos C57BL , Proteômica , Células Vero , Zika virus/fisiologia , Infecção por Zika virus/imunologia
7.
PLoS One ; 18(1): e0280392, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649304

RESUMO

For coronavirus disease 2019 (COVID-19), a pandemic disease characterized by strong immune dysregulation in severe patients, convenient and efficient monitoring of the host immune response is critical. Human hosts respond to viral and bacterial infections in different ways, the former is characterized by the activation of interferon stimulated genes (ISGs) such as IFI27, while the latter is characterized by the activation of anti-bacterial associated genes (ABGs) such as S100A12. This two-tiered innate immune response has not been examined in COVID-19. In this study, the activation patterns of this two-tiered innate immune response represented by IFI27 and S100A12 were explored based on 1421 samples from 17 transcriptome datasets derived from the blood of COVID-19 patients and relevant controls. It was found that IFI27 activation occurred in most of the symptomatic patients and displayed no correlation with disease severity, while S100A12 activation was more restricted to patients under severe and critical conditions with a stepwise activation pattern. In addition, most of the S100A12 activation was accompanied by IFI27 activation. Furthermore, the activation of IFI27 was most pronounced within the first week of symptom onset, but generally waned after 2-3 weeks. On the other hand, the activation of S100A12 displayed no apparent correlation with disease duration and could last for several months in certain patients. These features of the two-tiered innate immune response can further our understanding on the disease mechanism of COVID-19 and may have implications to the clinical triage. Development of a convenient two-gene protocol for the routine serial monitoring of this two-tiered immune response will be a valuable addition to the existing laboratory tests.


Assuntos
COVID-19 , Imunidade Inata , Humanos , COVID-19/genética , COVID-19/imunologia , Marcadores Genéticos , Imunidade Inata/genética , Interferons , Proteína S100A12/genética
10.
In Vivo ; 37(1): 70-78, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593041

RESUMO

BACKGROUND/AIM: The manifestation and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections show a clear correlation to the age of a patient. The younger a person, the less likely the infection results in significant illness. To explore the immunological characteristics behind this phenomenon, we studied the course of SARS-CoV-2 infections in 11 households, including 8 children and 6 infants/neonates of women who got infected with SARS-CoV-2 during pregnancy. MATERIALS AND METHODS: We investigated the immune responses of peripheral blood mononuclear cells (PBMCs), umbilical cord blood mononuclear cells (UCBCs), and T cells against spike and nucleocapsid antigens of SARS-COV-2 by flow cytometry and cytokine secretion assays. RESULTS: Upon peptide stimulation, UCBC from neonates showed a strongly reduced IFN-γ production, as well as lower levels of IL-5, IL-13, and TNF-α alongside with decreased frequencies of surface CD137/PD-1 co-expressing CD4+ and CD+8 T cells compared with adult PBMCs. The PBMC response of older children instead was characterized by elevated frequencies of IFN-γ+ CD4+ T cells, but significantly lower levels of multiple cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, and TNF-α) and a marked shift of the CD4+/CD8+ T-cell ratio towards CD8+ T cells in comparison to adults. CONCLUSION: The increased severity of SARS-CoV-2 infections in adults could result from the strong cytokine production and lower potential to immunomodulate the excessive inflammation, while the limited IFN-γ production of responding T cells in infants/neonates and the additional higher frequencies of CD8+ T cells in older children may provide advantages during the course of a SARS-CoV-2 infection.


Assuntos
Antígenos Virais , COVID-19 , Citocinas , Adulto , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Citocinas/imunologia , Leucócitos Mononucleares/imunologia , Nucleocapsídeo/imunologia , SARS-CoV-2 , Fatores Etários , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos/imunologia
11.
In Vivo ; 37(1): 286-293, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593062

RESUMO

BACKGROUND/AIM: Vitamin D3 (VD3) affects the regulation of the immune system, including the differentiation and function of regulatory T-cells (Tregs). Tregs play an important role in maintaining immune homeostasis in patients with colorectal cancer (CRC). The effects of VD3 on Treg-associated immune function were investigated in Thai patients in the early stages of CRC. MATERIALS AND METHODS: Twenty-eight patients were randomized to one of two groups: Untreated or treatment with VD3 for 3 months. Whole blood samples were collected at baseline, and at 1 and 3 months. Peripheral blood mononuclear cells were isolated and the populations of forkhead box P3-positive Treg cells was analyzed by flow cytometry. The levels of Treg-associated cytokines, interleukin 10 (IL-10) and transforming growth factor beta 1 (TGF-ß1), were measured by enzyme-linked immunosorbent assays. RESULTS: Serum VD3 levels of the VD3-treated group were significantly increased at 1 (p=0.017) and 3 months (p<0.001) compared to the untreated control group. The mean percentage of Tregs was maintained between 1 and 3 months in the VD3-treated group. At 3 months, the untreated group had significantly lower Treg levels than the VD3-treated group (p=0.043). Serum IL-10 levels of the VD3-treated group were statistically increased at 1 month compared to the control group (p=0.032). No significant difference in serum TGF-ß1 levels was observed between the two groups. However, the TGF-ß1 level in the VD3-treated group at 1 month was lower than that of the control. CONCLUSION: Our findings suggest that VD3 supplementation can maintain immune responses in the early stages of CRC, helping to control Treg function. Therefore, VD3 should be supplemented to maintain immune homeostasis, especially in patients with vitamin D deficiency.


Assuntos
Colecalciferol , Neoplasias Colorretais , Linfócitos T Reguladores , Humanos , Colecalciferol/administração & dosagem , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/cirurgia , Suplementos Nutricionais , Homeostase , Interleucina-10/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta1/imunologia
12.
Viruses ; 15(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36680207

RESUMO

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all the previously emerged variants. The numerous mutations in Omicron's viral genome and its sub-lineages attribute it a larger amount of viral fitness, owing to the alteration of the transmission and pathophysiology of the virus. With a rapid change to the viral structure, Omicron and its sub-variants, namely BA.1, BA.2, BA.3, BA.4, and BA.5, dominate the community with an ability to escape the neutralization efficiency induced by prior vaccination or infections. Similarly, several recombinant sub-variants of Omicron, namely XBB, XBD, and XBF, etc., have emerged, which a better understanding. This review mainly entails the changes to Omicron and its sub-lineages due to it having a higher number of mutations. The binding affinity, cellular entry, disease severity, infection rates, and most importantly, the immune evading potential of them are discussed in this review. A comparative analysis of the Delta variant and the other dominating variants that evolved before Omicron gives the readers an in-depth understanding of the landscape of Omicron's transmission and infection. Furthermore, this review discusses the range of neutralization abilities possessed by several approved antiviral therapeutic molecules and neutralizing antibodies which are functional against Omicron and its sub-variants. The rapid evolution of the sub-variants is causing infections, but the broader aspect of their transmission and neutralization has not been explored. Thus, the scientific community should adopt an elucidative approach to obtain a clear idea about the recently emerged sub-variants, including the recombinant variants, so that effective neutralization with vaccines and drugs can be achieved. This, in turn, will lead to a drop in the number of cases and, finally, an end to the pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/terapia , COVID-19/virologia , Mutação , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus , Evasão da Resposta Imune
13.
Viruses ; 15(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36680224

RESUMO

The influenza neuraminidase (NA) is a promising target for next-generation vaccines. Protection induced by vaccination with the computationally optimized broadly reactive NA antigen (N1-I COBRA NA) was characterized in both influenza serologically naive and pre-immune ferret models following H1N1 (A/California/07/2009, CA/09) or H5N1 (A/Vietnam/1203/2004, Viet/04) influenza challenges. The N1-I COBRA NA vaccine elicited antibodies with neutralizing ELLA activity against both seasonal and pandemic H1N1 influenza, as well as the H5N1 influenza virus. In both models, N1-I COBRA NA-vaccinated ferrets that were challenged with CA/09 virus had similar morbidity (weight loss and clinical symptoms) as ferrets vaccinated with the CA/09 HA control vaccine. There were significantly reduced viral titers compared to the mock-vaccinated control animals. Ferrets vaccinated with N1-I COBRA NA or Viet/04 NA vaccines were protected against the H5N1 virus infection with minimal clinical symptoms and negligible weight loss. In contrast, ferrets vaccinated with the CA/09 NA vaccine lost ~10% of their original body weight with 25% mortality. Vaccination with either HA or NA vaccines did not inhibit contact transmission of CA/09 virus to naïve cage mates. Overall, the N1-I COBRA vaccine elicited protective immune responses against both H1N1 and H5N1 infections and partially mitigated disease in contact-transmission receiving ferrets. These results indicate that the N1-I COBRA NA performed similarly to the CA/09 HA and NA positive controls. Therefore, the N1-I COBRA NA alone induces protection against viruses from both H5N1 and H1N1 subtypes, indicating its value as a vaccine component in broadly protective influenza vaccines.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Anticorpos Antivirais , Furões , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vacinas contra Influenza/imunologia , Neuraminidase , Infecções por Orthomyxoviridae/prevenção & controle
15.
N Engl J Med ; 388(3): 214-227, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36652353

RESUMO

BACKGROUND: The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. METHODS: In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-µg doses of the BNT162b2 vaccine were randomly assigned to receive 30 µg or 60 µg of BNT162b2, 30 µg or 60 µg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 µg (15 µg of BNT162b2 + 15 µg of monovalent BA.1) or 60 µg (30 µg of BNT162b2 + 30 µg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 µg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 µg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. RESULTS: A total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 µg and 60 µg) and monovalent BA.1 (60 µg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 µg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 µg) were also noninferior to BNT162b2 (30 µg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 µg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-µg bivalent BA.1 than with 30-µg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 µg). Adverse events were more common in the 30-µg monovalent-BA.1 (8.5%) and 60-µg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). CONCLUSIONS: The candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 µg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.).


Assuntos
Vacina BNT162 , COVID-19 , SARS-CoV-2 , Vacinas Combinadas , Humanos , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacina BNT162/efeitos adversos , Vacina BNT162/imunologia , Vacina BNT162/uso terapêutico , COVID-19/genética , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Vacinação , Vacinas Combinadas/uso terapêutico , Pessoa de Meia-Idade
16.
Cell Transplant ; 32: 9636897221148775, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36661068

RESUMO

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease associated with impaired organ functions that can seriously affect the daily life of patients. Recent SLE therapies frequently elicit adverse reactions and side effects in patients, and clinical heterogeneity is considerable. Mesenchymal stromal cells (MSCs) have anti-inflammatory, tissue repair, and immunomodulatory properties. Their ability to treat autoimmune diseases largely depends on secreted extracellular vesicles, especially exosomes. The effects of exosomes and microRNAs (miRNAs) on SLE have recently attracted interest. This review summarizes the applications of MSCs derived from bone marrow, adipocyte tissue, umbilical cord, synovial membrane, and gingival tissue, as well as exosomes to treating SLE and the key roles of miRNAs. The efficacy of MSCs infusion in SLE patients with impaired autologous MSCs are reviewed, and the potential of exosomes and their contents as drug delivery vectors for treating SLE and other autoimmune diseases in the future are briefly described.


Assuntos
Exossomos , Lúpus Eritematoso Sistêmico , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Exossomos/genética , Exossomos/imunologia , Vesículas Extracelulares/genética , Vesículas Extracelulares/imunologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , MicroRNAs/genética , MicroRNAs/imunologia , Células-Tronco Mesenquimais/imunologia
17.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36674732

RESUMO

MiRNAs are critical regulators of numerous physiological and pathological processes. Ascosphaera apis exclusively infects bee larvae and causes chalkbrood disease. However, the function and mechanism of miRNAs in the bee larval response to A. apis infection is poorly understood. Here, ame-miR-34, a previously predicted miRNA involved in the response of Apis mellifera larvae to A. apis invasion, was subjected to molecular validation, and overexpression and knockdown were then conducted to explore the regulatory functions of ame-miR-34 in larval body weight and immune response. Stem-loop RT-PCR and Sanger sequencing confirmed the authenticity of ame-miR-34 in the larval gut of A. mellifera. RT-qPCR results demonstrated that compared with that in the uninfected larval guts, the expression level of ame-miR-34 was significantly downregulated (p < 0.001) in the guts of A. apis-infected 4-, 5-, and 6-day-old larvae, indicative of the remarkable suppression of host ame-miR-34 due to A. apis infection. In comparison with the corresponding negative control (NC) groups, the expression level of ame-miR-34 in the larval guts in the mimic-miR-34 group was significantly upregulated (p < 0.001), while that in the inhibitor-miR-34 group was significantly downregulated (p < 0.01). Similarly, effective overexpression and knockdown of ame-miR-34 were achieved. In addition, the body weights of 5- and 6-day-old larvae were significantly increased compared with those in the mimic-NC group; the weights of 5-day-old larvae in the inhibitor-miR-34 group were significantly decreased in comparison with those in the inhibitor-NC group, while the weights of 4- and 6-day-old larvae in the inhibitor-miR-34 group were significantly increased, indicating the involvement of ame-miR-34 in modulating larval body weight. Furthermore, the expression levels of both hsp and abct in the guts of A. apis-infected 4-, 5-, and 6-day-old larvae were significantly upregulated after ame-miR-34 overexpression. In contrast, after ame-miR-34 knockdown, the expression levels of the aforementioned two key genes in the A. apis-infected 4-, 5-, and 6-day-old larval guts were significantly downregulated. Together, the results demonstrated that effective overexpression and knockdown of ame-miR-34 in both noninfected and A. apis-infected A. mellifera larval guts could be achieved by the feeding method, and ame-miR-34 exerted a regulatory function in the host immune response to A. apis invasion through positive regulation of the expression of hsp and abct. Our findings not only provide a valuable reference for the functional investigation of bee larval miRNAs but also reveal the regulatory role of ame-miR-34 in A. mellifera larval weight and immune response. Additionally, the results of this study may provide a promising molecular target for the treatment of chalkbrood disease.


Assuntos
Arthrodermataceae , Abelhas , MicroRNAs , Animais , Abelhas/genética , Abelhas/imunologia , Abelhas/microbiologia , Peso Corporal , Imunidade , Larva/imunologia , MicroRNAs/genética , MicroRNAs/metabolismo , Arthrodermataceae/fisiologia
18.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36674531

RESUMO

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.


Assuntos
Aborto Espontâneo , Tireoidite Autoimune , Animais , Feminino , Camundongos , Gravidez , Autoanticorpos , Epitopos , Doença de Hashimoto , Imunoglobulina G , Fosfopiruvato Hidratase , Projetos Piloto , Tireoidite Autoimune/complicações , Aborto Espontâneo/imunologia
19.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36674524

RESUMO

Tick-borne encephalitis (TBE) is an emerging zoonosis that may cause long-term neurological sequelae or even death. Thus, there is a growing interest in understanding the factors of TBE pathogenesis. Viral genetic determinants may greatly affect the severity and consequences of TBE. In this study, nonstructural protein 1 (NS1) of the tick-borne encephalitis virus (TBEV) was tested as such a determinant. NS1s of three strains with similar neuroinvasiveness belonging to the European, Siberian and Far-Eastern subtypes of TBEV were studied. Transfection of mouse cells with plasmids encoding NS1 of the three TBEV subtypes led to different levels of NS1 protein accumulation in and secretion from the cells. NS1s of TBEV were able to trigger cytokine production either in isolated mouse splenocytes or in mice after delivery of NS1 encoding plasmids. The profile and dynamics of TNF-α, IL-6, IL-10 and IFN-γ differed between the strains. These results demonstrated the involvement of TBEV NS1 in triggering an immune response and indicated the diversity of NS1 as one of the genetic factors of TBEV pathogenicity.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Proteínas não Estruturais Virais , Animais , Camundongos , Vírus da Encefalite Transmitidos por Carrapatos/classificação , Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Encefalite Transmitida por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/virologia , Interleucina-10/genética , Zoonoses , Proteínas não Estruturais Virais/metabolismo
20.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36675034

RESUMO

Insects rely only on their innate immune system to protect themselves from pathogens. Antimicrobial peptide (AMP) production is the main immune reaction in insects. In Drosophila melanogaster, the reaction is regulated mainly by the Toll and immune deficiency (IMD) pathways. Spaetzle proteins, activated by immune signals from upstream components, bind to Toll proteins, thus, activating the Toll pathway, which in turn, induces AMP genes. Previous studies have shown the difference in immune systems related to Toll and IMD pathways between D. melanogaster and Tribolium castaneum. In T. castaneum, nine Toll and seven spaetzle (spz) genes were identified. To extend our understanding of AMP production by T. castaneum, we conducted functional assays of Toll and spaetzle genes related to Toll-pathway-dependent AMP gene expression in T. castaneum under challenge with bacteria or budding yeast. The results revealed that Toll3 and Toll4 double-knockdown and spz7 knockdown strongly and moderately reduced the Toll-pathway-dependent expression of AMP genes, respectively. Moreover, Toll3 and Toll4 double-knockdown pupae more rapidly succumbed to entomopathogenic bacteria than the control pupae, but spz7 knockdown pupae did not. The results suggest that Toll3 and Toll4 play a large role in Toll-pathway-dependent immune reactions, whereas spz7 plays a small part.


Assuntos
Peptídeos Antimicrobianos , Imunidade Inata , Infecções , Tribolium , Animais , Besouros/genética , Besouros/imunologia , Besouros/microbiologia , Expressão Gênica , Tribolium/genética , Tribolium/imunologia , Tribolium/microbiologia , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/imunologia , Imunidade Inata/imunologia , Infecções/imunologia , Infecções/microbiologia
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