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Front Immunol ; 13: 891816, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911710


An important number of studies have been conducted on the potential association between human leukocyte antigen (HLA) genes and COVID-19 susceptibility and severity since the beginning of the pandemic. However, case-control and peptide-binding prediction methods tended to provide inconsistent conclusions on risk and protective HLA alleles, whereas some researchers suggested the importance of considering the overall capacity of an individual's HLA Class I molecules to present SARS-CoV-2-derived peptides. To close the gap between these approaches, we explored the distributions of HLA-A, -B, -C, and -DRB1 1st-field alleles in 142 Iranian patients with COVID-19 and 143 ethnically matched healthy controls, and applied in silico predictions of bound viral peptides for each individual's HLA molecules. Frequency comparison revealed the possible predisposing roles of HLA-A*03, B*35, and DRB1*16 alleles and the protective effect of HLA-A*32, B*58, B*55, and DRB1*14 alleles in the viral infection. None of these results remained significant after multiple testing corrections, except HLA-A*03, and no allele was associated with severity, either. Compared to peptide repertoires of individual HLA molecules that are more likely population-specific, the overall coverage of virus-derived peptides by one's HLA Class I molecules seemed to be a more prominent factor associated with both COVID-19 susceptibility and severity, which was independent of affinity index and threshold chosen, especially for people under 60 years old. Our results highlight the effect of the binding capacity of different HLA Class I molecules as a whole, and the more essential role of HLA-A compared to HLA-B and -C genes in immune responses against SARS-CoV-2 infection.

COVID-19 , Antígenos de Histocompatibilidade Classe I , Proteínas Virais , COVID-19/genética , Antígenos HLA-A/genética , Antígenos HLA-A/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Ligação Proteica , SARS-CoV-2 , Proteínas Virais/metabolismo
J Med Virol ; 94(10): 4611-4627, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35689351


The field of immunometabolism investigates and describes the effects of metabolic rewiring in immune cells throughout activation and the fates of these cells. Recently, it has been appreciated that immunometabolism plays an essential role in the progression of viral infections, cancer, and autoimmune diseases. Regarding COVID-19, the aberrant immune response underlying the progression of diseases establishes two major respiratory pathologies, including acute respiratory distress syndrome (ARDS) or pneumonia-induced acute lung injury (ALI). Both innate and adaptive immunity (T cell-based) were impaired in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Current findings have deciphered that macrophages (innate immune cells) are involved in the inflammatory response seen in COVID-19. It has been demonstrated that immune system cells can change metabolic reprogramming in some conditions, including autoimmune diseases, cancer, and infectious disease, including COVID-19. The growing findings on metabolic reprogramming in COVID-19 allow an exploration of metabolites with immunomodulatory properties as future therapies to combat this hyperinflammatory response. The elucidation of the exact role and mechanism underlying this metabolic reprograming in immune cells could help apply more precise approaches to initial diagnosis, prognosis, and in-hospital therapy. This report discusses the latest findings from COVID-19 on host metabolic reprogramming and immunometabolic responses.

Doenças Autoimunes , COVID-19 , Neoplasias , Síndrome do Desconforto Respiratório , Humanos , Imunidade Inata , SARS-CoV-2
Acta Trop ; 227: 106298, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34971566


BACKGROUND: The protective effect of immunization using Iranian Lizard Leishmania (ILL) mixed with CpG oligodeoxynucleotides (CpG-ODN) was demonstrated in a previous study. Here, we report the effect of leishmanization using ILL mixed with chitin microparticles (CMPs) as an adjuvant against L. major infection in BALB/c mice. METHODS: Briefly, 2 × 107 live ILL were mixed with 10 µg CMPs (<40 µm in size) (ILL+CMP) and were injected subcutaneously into the right footpad of BALB/c mice. Three control groups were included in the study and received ILL, chitin, and PBS respectively. Three weeks later, mice were challenged with 2 × 105 live L. majorEGFP promastigotes, which were inoculated into the left footpad. The infection course was monitored using footpad swelling measurement and in vivo imaging. Eleven weeks after the challenge, all mice were sacrificed and parasite burden was measured in the spleen and the draining lymph node using three different methods including real-time PCR, flow cytometry, and direct fluorescent microscopy. In addition, cytokines levels (IFN-γ and IL-10), and nitric oxide production were assayed in splenocytes. RESULTS: Mice immunized with ILL+CMP had a smaller footpad diameter in comparison to control groups and notably, no lesion was developed at the inoculation site. Additionally, in vivo imaging study revealed that there was no detectable fluorescence in the ILL+CMP group footpad by the end of the tenth week. This finding was confirmed by three methods used for parasite burden assays. Moreover, higher IFN-γ level was observed in mice immunized with ILL+CMP in comparison with other groups. On the other hand, nitric oxide concentration was higher in the ILL control group. CONCLUSION: ILL mixed with chitin microparticles is an effective vaccine against leishmaniasis in BALB/c mice. This vaccine is able to induce an adequate immune response to decrease the parasite burden and prevent lesion formation. Further studies are needed to evaluate long-lasting immunity, especially in experimental outbreed models.

Leishmania major , Vacinas contra Leishmaniose , Leishmaniose Cutânea , Lagartos , Animais , Anticorpos Antiprotozoários , Quitina , Irã (Geográfico) , Leishmaniose Cutânea/parasitologia , Camundongos , Camundongos Endogâmicos BALB C
J Neuroimmunol ; 358: 577640, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34224949


Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases.

Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Autoimunidade/imunologia , Exossomos/imunologia , MicroRNAs/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/terapia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , MicroRNAs/administração & dosagem , Esclerose Múltipla/imunologia , Esclerose Múltipla/terapia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/terapia
Front Immunol ; 11: 1725, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193290


Background and Objectives: The live non-pathogenic Leishmania tarantolae has recently provided a promising approach as an effective vaccine candidate against experimental leishmaniasis (ILL). Here, we evaluated the immunoprotective potential of the live Iranian Lizard Leishmania mixed with CpG adjuvant against L. major infection in BALB/c mice. Methods: Four groups of female BALB/c mice were included in the study. The first and second groups received PBS and CpG, respectively. The immunized groups received 2 × 105 ILL promastigotes and the CpG-mixed ILL (ILL+CpG). Injections were performed subcutaneously in the right footpad. Three weeks later, all mice were challenged with 2 × 105 metacyclic promastigotes of Leishmania majorEGFP ; inoculation was done in the left footpad. The measurement of footpad swelling and in vivo fluorescent imaging were used to evaluate disease progress during infection course. Eight weeks after challenge, all mice were sacrificed and the cytokines levels (IFN-γ, IL-4, and IL-10) and sera antibodies concentrations (IgG2a and IgG1) using ELISA assay, nitric oxide production using Griess assay, and arginase activity in cultured splenocytes, were measured. In addition, direct fluorescent microscopy analysis and qPCR assay were used to quantify the splenic parasite burden. Result: The results showed that mice immunized with ILL+CpG were protected against the development of the dermal lesion. Moreover, they showed a significant reduction in the parasite load, in comparison to the control groups. The observed protection was associated with higher production of IFN-γ, as well as a reduction in IL-4 level. Additionally, the results demonstrated that arginase activity was decreased in ILL+CpG group compared to other groups. Conclusion: Immunization using ILL+CpG induces a protective immunity; indicating that ILL with an appropriate adjuvant would be a suitable choice for vaccination against leishmaniasis.

Adjuvantes Imunológicos/farmacologia , Leishmania major/imunologia , Vacinas contra Leishmaniose/farmacologia , Leishmaniose Cutânea/prevenção & controle , Lagartos/parasitologia , Oligodesoxirribonucleotídeos/farmacologia , Pele/efeitos dos fármacos , Vacinas Vivas não Atenuadas/farmacologia , Animais , Anticorpos Antiprotozoários/sangue , Arginase/metabolismo , Células Cultivadas , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Imunização , Imunogenicidade da Vacina , Leishmaniose Cutânea/sangue , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Camundongos Endogâmicos BALB C , Carga Parasitária , Pele/imunologia , Pele/parasitologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Baço/parasitologia , Vacinas Vivas não Atenuadas/imunologia