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1.
Front Immunol ; 15: 1357360, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994357

RESUMO

Background: The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored. Methods: An observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination. Results: Among 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1ß, IL-5, IL-7, and TNF-ß was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1ß was significantly higher in the TB/Prex-SCoV-2 group than the TB group. Conclusion: TB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.


Assuntos
COVID-19 , Citocinas , SARS-CoV-2 , Tuberculose Pulmonar , Humanos , COVID-19/imunologia , COVID-19/sangue , Masculino , Feminino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/sangue , Citocinas/sangue , Citocinas/imunologia , Brasil/epidemiologia
2.
Front Immunol ; 15: 1407237, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947329

RESUMO

Introduction: Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers. Methods: We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria. Results: qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo. Discussion: Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.


Assuntos
Aeromonas hydrophila , Carpas , Citocinas , Eritrócitos , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Animais , Carpas/imunologia , Carpas/microbiologia , Eritrócitos/imunologia , Eritrócitos/metabolismo , Citocinas/metabolismo , Citocinas/imunologia , Aeromonas hydrophila/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Fagocitose/imunologia , Moléculas com Motivos Associados a Patógenos/imunologia , Imunidade Inata
3.
Front Immunol ; 15: 1419951, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947335

RESUMO

The Suppressor of Cytokine Signaling (SOCS) family proteins are important negative regulators of cytokine signaling. SOCS1 is the prototypical member of the SOCS family and functions in a classic negative-feedback loop to inhibit signaling in response to interferon, interleukin-12 and interleukin-2 family cytokines. These cytokines have a critical role in orchestrating our immune defence against viral pathogens and cancer. The ability of SOCS1 to limit cytokine signaling positions it as an important immune checkpoint, as evidenced by the detection of detrimental SOCS1 variants in patients with cytokine-driven inflammatory and autoimmune disease. SOCS1 has also emerged as a key checkpoint that restricts anti-tumor immunity, playing both a tumor intrinsic role and impacting the ability of various immune cells to mount an effective anti-tumor response. In this review, we describe the mechanism of SOCS1 action, focusing on the role of SOCS1 in autoimmunity and cancer, and discuss the potential for new SOCS1-directed cancer therapies that could be used to enhance adoptive immunotherapy and immune checkpoint blockade.


Assuntos
Homeostase , Inflamação , Neoplasias , Proteína 1 Supressora da Sinalização de Citocina , Humanos , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/genética , Neoplasias/imunologia , Neoplasias/terapia , Homeostase/imunologia , Inflamação/imunologia , Animais , Transdução de Sinais , Autoimunidade , Citocinas/metabolismo , Citocinas/imunologia
4.
Front Immunol ; 15: 1424374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966641

RESUMO

At the beginning of the COVID-19 pandemic those with underlying chronic lung conditions, including tuberculosis (TB), were hypothesized to be at higher risk of severe COVID-19 disease. However, there is inconclusive clinical and preclinical data to confirm the specific risk SARS-CoV-2 poses for the millions of individuals infected with Mycobacterium tuberculosis (M.tb). We and others have found that compared to singly infected mice, mice co-infected with M.tb and SARS-CoV-2 leads to reduced SARS-CoV-2 severity compared to mice infected with SARS-CoV-2 alone. Consequently, there is a large interest in identifying the molecular mechanisms responsible for the reduced SARS-CoV-2 infection severity observed in M.tb and SARS-CoV-2 co-infection. To address this, we conducted a comprehensive characterization of a co-infection model and performed mechanistic in vitro modeling to dynamically assess how the innate immune response induced by M.tb restricts viral replication. Our study has successfully identified several cytokines that induce the upregulation of anti-viral genes in lung epithelial cells, thereby providing protection prior to challenge with SARS-CoV-2. In conclusion, our study offers a comprehensive understanding of the key pathways induced by an existing bacterial infection that effectively restricts SARS-CoV-2 activity and identifies candidate therapeutic targets for SARS-CoV-2 infection.


Assuntos
COVID-19 , Coinfecção , Imunidade Inata , Mycobacterium tuberculosis , SARS-CoV-2 , COVID-19/imunologia , Animais , Mycobacterium tuberculosis/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Camundongos , Coinfecção/imunologia , Humanos , Tuberculose/imunologia , Tuberculose/microbiologia , Citocinas/metabolismo , Citocinas/imunologia , Modelos Animais de Doenças , Índice de Gravidade de Doença , Pulmão/imunologia , Pulmão/virologia , Pulmão/microbiologia , Pulmão/patologia , Replicação Viral , Camundongos Endogâmicos C57BL , Feminino
5.
Sci Immunol ; 9(97): eadl1965, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968336

RESUMO

Schistosomiasis is an infection caused by contact with Schistosoma-contaminated water and affects more than 230 million people worldwide with varying morbidity. The roles of T helper 2 (TH2) cells and regulatory immune responses in chronic infection are well documented, but less is known about human immune responses during acute infection. Here, we comprehensively map immune responses during controlled human Schistosoma mansoni infection using male or female cercariae. Immune responses to male or female parasite single-sex infection were comparable. An early TH1-biased inflammatory response was observed at week 4 after infection, which was particularly apparent in individuals experiencing symptoms of acute schistosomiasis. By week 8 after infection, inflammatory responses were followed by an expansion of TH2 and regulatory cell subsets. This study demonstrates the shift from TH1 to both TH2 and regulatory responses, typical of chronic schistosomiasis, in the absence of egg production and provides immunological insight into the clinical manifestations of acute schistosomiasis.


Assuntos
Schistosoma mansoni , Esquistossomose mansoni , Células Th2 , Humanos , Feminino , Animais , Masculino , Células Th2/imunologia , Esquistossomose mansoni/imunologia , Schistosoma mansoni/imunologia , Inflamação/imunologia , Adulto , Células Th1/imunologia , Adulto Jovem , Adolescente , Citocinas/imunologia , Esquistossomose/imunologia , Esquistossomose/parasitologia
6.
J Exp Med ; 221(9)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-38949638

RESUMO

Studies during the COVID-19 pandemic showed that children had heightened nasal innate immune responses compared with adults. To evaluate the role of nasal viruses and bacteria in driving these responses, we performed cytokine profiling and comprehensive, symptom-agnostic testing for respiratory viruses and bacterial pathobionts in nasopharyngeal samples from children tested for SARS-CoV-2 in 2021-22 (n = 467). Respiratory viruses and/or pathobionts were highly prevalent (82% of symptomatic and 30% asymptomatic children; 90 and 49% for children <5 years). Virus detection and load correlated with the nasal interferon response biomarker CXCL10, and the previously reported discrepancy between SARS-CoV-2 viral load and nasal interferon response was explained by viral coinfections. Bacterial pathobionts correlated with a distinct proinflammatory response with elevated IL-1ß and TNF but not CXCL10. Furthermore, paired samples from healthy 1-year-olds collected 1-2 wk apart revealed frequent respiratory virus acquisition or clearance, with mucosal immunophenotype changing in parallel. These findings reveal that frequent, dynamic host-pathogen interactions drive nasal innate immune activation in children.


Assuntos
COVID-19 , Imunidade Inata , SARS-CoV-2 , Humanos , Imunidade Inata/imunologia , Pré-Escolar , Lactente , COVID-19/imunologia , COVID-19/virologia , Criança , SARS-CoV-2/imunologia , Feminino , Masculino , Nasofaringe/imunologia , Nasofaringe/virologia , Nasofaringe/microbiologia , Carga Viral , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Mucosa Nasal/microbiologia , Citocinas/metabolismo , Citocinas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Adolescente , Nariz/imunologia , Nariz/virologia , Nariz/microbiologia , Coinfecção/imunologia , Coinfecção/virologia
7.
Front Immunol ; 15: 1347926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903517

RESUMO

Introduction: The HVTN 105 vaccine clinical trial tested four combinations of two immunogens - the DNA vaccine DNA-HIV-PT123, and the protein vaccine AIDSVAX B/E. All combinations induced substantial antibody and CD4+ T cell responses in many participants. We have now re-examined the intracellular cytokine staining flow cytometry data using the high-resolution SWIFT clustering algorithm, which is very effective for enumerating rare populations such as antigen-responsive T cells, and also determined correlations between the antibody and T cell responses. Methods: Flow cytometry samples across all the analysis batches were registered using the swiftReg registration tool, which reduces batch variation without compromising biological variation. Registered data were clustered using the SWIFT algorithm, and cluster template competition was used to identify clusters of antigen-responsive T cells and to separate these from constitutive cytokine producing cell clusters. Results: Registration strongly reduced batch variation among batches analyzed across several months. This in-depth clustering analysis identified a greater proportion of responders than the original analysis. A subset of antigen-responsive clusters producing IL-21 was identified. The cytokine patterns in each vaccine group were related to the type of vaccine - protein antigens tended to induce more cells producing IL-2 but not IFN-γ, whereas DNA vaccines tended to induce more IL-2+ IFN-γ+ CD4 T cells. Several significant correlations were identified between specific antibody responses and antigen-responsive T cell clusters. The best correlations were not necessarily observed with the strongest antibody or T cell responses. Conclusion: In the complex HVTN105 dataset, alternative analysis methods increased sensitivity of the detection of antigen-specific T cells; increased the number of identified vaccine responders; identified a small IL-21-producing T cell population; and demonstrated significant correlations between specific T cell populations and serum antibody responses. Multiple analysis strategies may be valuable for extracting the most information from large, complex studies.


Assuntos
Vacinas contra a AIDS , Linfócitos T CD4-Positivos , Citocinas , Citometria de Fluxo , Infecções por HIV , Humanos , Vacinas contra a AIDS/imunologia , Linfócitos T CD4-Positivos/imunologia , Citometria de Fluxo/métodos , Análise por Conglomerados , Infecções por HIV/imunologia , Infecções por HIV/virologia , Citocinas/metabolismo , Citocinas/imunologia , Imunidade Humoral , Anticorpos Anti-HIV/imunologia , Anticorpos Anti-HIV/sangue , HIV-1/imunologia , Vacinas de DNA/imunologia , Interleucinas/imunologia
8.
Front Immunol ; 15: 1352704, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895118

RESUMO

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). Objective: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp). Methods: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusion: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.


Assuntos
Dermatite Atópica , Imunoglobulina E , Serina Proteases , Staphylococcus epidermidis , Humanos , Staphylococcus epidermidis/imunologia , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Serina Proteases/imunologia , Serina Proteases/metabolismo , Adulto , Masculino , Feminino , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Proteínas de Bactérias/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Citocinas/metabolismo , Citocinas/imunologia , Linfócitos T/imunologia , Alérgenos/imunologia , Interleucina-33/imunologia , Pessoa de Meia-Idade
9.
J Med Virol ; 96(6): e29739, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899449

RESUMO

This longitudinal prospective controlled multicenter study aimed to monitor immunity generated by three exposures caused by breakthrough infections (BTI) after COVID-19-vaccination considering pre-existing cell-mediated immunity to common-corona-viruses (CoV) which may impact cellular reactivity against SARS-CoV-2. Anti-SARS-CoV-2-spike-IgG antibodies (anti-S-IgG) and cellular reactivity against Spike-(S)- and nucleocapsid-(N)-proteins were determined in fully-vaccinated (F) individuals who either experienced BTI (F+BTI) or had booster vaccination (F+Booster) compared to partially vaccinated (P+BTI) and unvaccinated (U) from 1 to 24 weeks post PCR-confirmed infection. High avidity anti-S-IgG were found in F+BTI compared to U, the latter exhibiting increased long-lasting pro-inflammatory cytokines to S-stimulation. CoV was associated with higher cellular reactivity in U, whereas no association was seen in F. The study illustrates the induction of significant S-specific cellular responses in F+BTI building-up basic immunity by three exposures. Only U seem to benefit from pre-existing CoV immunity but demonstrated inflammatory immune responses compared to F+BTI who immunologically benefit from enhanced humoral and cellular immunity after BTI. This study demonstrates that individuals with hybrid immunity from COVID-19-vaccination and BTI acquire a stable humoral and cellular immune response that is maintained for at least 6 months. Our findings corroborate recommendations by health authorities to build on basic immunity by three S-protein exposures.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Masculino , Feminino , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina G/sangue , Estudos Longitudinais , Vacinação , Fosfoproteínas/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Idoso , Imunização Secundária , Citocinas/imunologia , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacinas de mRNA/imunologia , Infecções Irruptivas
10.
Immun Inflamm Dis ; 12(6): e1321, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888451

RESUMO

BACKGROUND: For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the immunomodulatory capabilities of Succinate Coenzyme A ligase beta-like protein (SUCLA-ß) derived from Trichinella spiralis, a crucial excretory product of this parasite. OBJECTIVE: To explore the therapeutic potential of SUCLA-ß in alleviating and controlling ovalbumin (OVA)-induced allergic asthma, as well as its influence on host immune modulation. METHODS: In this research, we utilized the rTs-SUCLA-ß protein derived from T. spiralis to investigate its potential in mitigating airway inflammation in a murine model of asthma induced by OVA sensitization/stimulation, both pre- and post-challenge. The treatment's efficacy was assessed by quantifying the extent of inflammation in the lungs. RESULTS: Treatment with rTs-SUCLA-ß demonstrated efficacy in ameliorating OVA-induced airway inflammation, as evidenced by a reduction in eosinophil infiltration, levels of OVA-specific Immunoglobulin E, interferon-γ, interleukin (IL)-9, and IL-17A, along with an elevation in IL-10. The equilibrium between Th17 and Treg cells plays a pivotal role in modulating the abundance of inflammatory cells within the organism, thereby ameliorating inflammation and alleviating symptoms associated with allergic asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Our data revealed that T. spiralis-derived Ts-SUCLA-ß protein may inhibit the allergic airway inflammation by regulating host immune responses.


Assuntos
Asma , Proteínas de Helminto , Ovalbumina , Trichinella spiralis , Trichinella spiralis/imunologia , Animais , Asma/imunologia , Asma/tratamento farmacológico , Camundongos , Ovalbumina/imunologia , Proteínas de Helminto/imunologia , Proteínas de Helminto/farmacologia , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Feminino , Citocinas/metabolismo , Citocinas/imunologia , Imunoglobulina E/imunologia , Pulmão/imunologia , Pulmão/parasitologia , Pulmão/patologia , Linfócitos T Reguladores/imunologia , Hipersensibilidade/imunologia , Hipersensibilidade/tratamento farmacológico , Células Th17/imunologia
11.
Int J Nanomedicine ; 19: 5793-5812, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882535

RESUMO

This review article discusses the potential of nanomaterials in targeted therapy and immunomodulation for stroke-induced immunosuppression. Although nanomaterials have been extensively studied in various biomedical applications, their specific use in studying and addressing immunosuppression after stroke remains limited. Stroke-induced neuroinflammation is characterized by T-cell-mediated immunodepression, which leads to increased morbidity and mortality. Key observations related to immunodepression after stroke, including lymphopenia, T-cell dysfunction, regulatory T-cell imbalance, and cytokine dysregulation, are discussed. Nanomaterials, such as liposomes, micelles, polymeric nanoparticles, and dendrimers, offer advantages in the precise delivery of drugs to T cells, enabling enhanced targeting and controlled release of immunomodulatory agents. These nanomaterials have the potential to modulate T-cell function, promote neuroregeneration, and restore immune responses, providing new avenues for stroke treatment. However, challenges related to biocompatibility, stability, scalability, and clinical translation need to be addressed. Future research efforts should focus on comprehensive studies to validate the efficacy and safety of nanomaterial-based interventions targeting T cells in stroke-induced immunosuppression. Collaborative interdisciplinary approaches are necessary to advance the field and translate these innovative strategies into clinical practice, ultimately improving stroke outcomes and patient care.


Assuntos
Nanoestruturas , Acidente Vascular Cerebral , Linfócitos T , Animais , Humanos , Citocinas/metabolismo , Citocinas/imunologia , Nanomedicina , Nanopartículas/química , Nanoestruturas/química , Acidente Vascular Cerebral/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos
12.
Mem Inst Oswaldo Cruz ; 119: e240013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38896633

RESUMO

BACKGROUND: The impact of Schistosoma mansoni infection over the immune response and the mechanisms involved in pathogenesis are not yet completely understood. OBJECTIVES: This study aimed to evaluate the expression of innate immune receptors in three distinct mouse lineages (BALB/c, C57BL/6 and Swiss) during experimental S. mansoni infection with LE strain. METHODS: The parasite burden, intestinal tissue oogram and presence of hepatic granulomas were evaluated at 7- and 12-weeks post infection (wpi). The mRNA expression for innate Toll-like receptors, Nod-like receptors, their adaptor molecules, and cytokines were determined at 2, 7 and 12 wpi in the hepatic tissue by real-time quantitative polymerase chain reaction (qPCR). FINDINGS: Swiss mice showed 100% of survival, had lower parasite burden and intestinal eggs, while infected BALB/c and C57BL/6 presented 80% and 90% of survival, respectively, higher parasite burden and intestinal eggs. The three mouse lineages displayed distinct patterns in the expression of innate immune receptors, their adaptor molecules and cytokines, at 2 and 7 wpi. MAIN CONCLUSIONS: Our results suggest that the pathogenesis of S. mansoni infection is related to a dynamic early activation of innate immunity receptors and cytokines important for the control of developing worms.


Assuntos
Citocinas , Imunidade Inata , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Esquistossomose mansoni , Animais , Esquistossomose mansoni/imunologia , Imunidade Inata/imunologia , Citocinas/imunologia , Camundongos , Schistosoma mansoni/imunologia , Modelos Animais de Doenças , Feminino , Receptores Toll-Like/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Contagem de Ovos de Parasitas , Masculino , RNA Mensageiro , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia
13.
Front Immunol ; 15: 1398369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835759

RESUMO

Introduction: Although many studies have underscored the importance of T cells, phenotypically and functionally, fewer have studied the functions of myeloid cells in COVID disease. In particular, the potential role of myeloid cells such as monocytes and low-density neutrophils (LDNs) in innate responses and particular in the defense against secondary bacterial infections has been much less documented. Methods: Here, we compared, in a longitudinal study, healthy subjects, idiopathic fibrosis patients, COVID patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) and patients in ICU hospitalized for other reasons (non-COV-ICU). Results: We show that COVID patients have an increased proportion of low-density neutrophils (LDNs), which produce high levels of proteases (particularly, NE, MMP-8 and MMP-9) (unlike non-COV-ICU patients), which are partly responsible for causing type II alveolar cell damage in co-culture experiments. In addition, we showed that M- and ICU-COVID monocytes had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, an important pathogen colonizing COVID patients in ICU, as assessed by an impaired secretion of myeloid cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid cytokines (in particular type 2/type 3) levels remained high, both basally and post PAO1 infection, as reflected by the unimpaired capacity of T cells to proliferate, when stimulated with anti-CD3/CD28 beads. Discussion: Overall, our results demonstrate that COVID circulatory T cells have a biased type 2/3 phenotype, unconducive to proper anti-viral responses and that myeloid cells have a dual deleterious phenotype, through their LDN-mediated damaging effect on alveolar cells and their impaired responsiveness (monocyte-mediated) towards bacterial pathogens such as P. aeruginosa.


Assuntos
COVID-19 , Monócitos , Neutrófilos , Infecções por Pseudomonas , Pseudomonas aeruginosa , SARS-CoV-2 , Humanos , COVID-19/imunologia , Pseudomonas aeruginosa/imunologia , Monócitos/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Infecções por Pseudomonas/imunologia , Neutrófilos/imunologia , Idoso , Citocinas/metabolismo , Citocinas/imunologia , Adulto , Estudos Longitudinais , Leucócitos Mononucleares/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/microbiologia
14.
Front Immunol ; 15: 1405215, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38868763

RESUMO

Chronic inflammatory skin diseases are multifactorial diseases that combine genetic predisposition, environmental triggers, and metabolic disturbances associated with abnormal immune responses. From an immunological perspective, the better understanding of their physiopathology has demonstrated a large complex network of immune cell subsets and related cytokines that interact with both epidermal and dermal cells. For example, in type-1-associated diseases such as alopecia areata, vitiligo, and localized scleroderma, recent evidence suggests the presence of a type-2 inflammation that is well known in atopic dermatitis. Whether this type-2 immune response has a protective or detrimental impact on the development and chronicity of these diseases remains to be fully elucidated, highlighting the need to better understand its involvement for the management of patients. This mini-review explores recent insights regarding the potential role of type-2-related immunity in alopecia areata, vitiligo, and localized scleroderma.


Assuntos
Vitiligo , Humanos , Vitiligo/imunologia , Animais , Alopecia em Áreas/imunologia , Células Th2/imunologia , Citocinas/metabolismo , Citocinas/imunologia , Dermatite Atópica/imunologia , Dermatite Atópica/etiologia , Esclerodermia Localizada/imunologia , Inflamação/imunologia , Pele/imunologia , Pele/patologia
15.
Transl Psychiatry ; 14(1): 254, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866753

RESUMO

Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis is increasingly recognized, there is a lack of comprehensive understanding regarding the involvement of innate and adaptive immune cells. To address this gap, we conducted a multicenter case-control study involving 121 participants matched for sex and age. These participants had either an active (or current) major depressive episode (MDE) (39 cases) or a remitted MDE (40 cases), including individuals with major depressive disorder or bipolar disorder. We compared these 79 patients to 42 healthy controls (HC), analyzing their immunological profiles. In blood samples, we determined the complete cell count and the monocyte subtypes and lymphocyte T-cell populations using flow cytometry. Additionally, we measured a panel of cytokines, chemokines, and neurotrophic factors in the plasma. Compared with HC, people endorsing a current MDE showed monocytosis (p = 0.001), increased high-sensitivity C-reactive protein (p = 0.002), and erythrocyte sedimentation rate (p = 0.003), and an altered proportion of specific monocyte subsets. CD4 lymphocytes presented increased median percentages of activation markers CD69+ (p = 0.007) and exhaustion markers PD1+ (p = 0.013) and LAG3+ (p = 0.014), as well as a higher frequency of CD4+CD25+FOXP3+ regulatory T cells (p = 0.003). Additionally, patients showed increased plasma levels of sTREM2 (p = 0.0089). These changes are more likely state markers, indicating the presence of an ongoing inflammatory response during an active MDE. The Random Forest model achieved remarkable classification accuracies of 83.8% for MDE vs. HC and 70% for differentiating active and remitted MDE. Interestingly, the cluster analysis identified three distinct immunological profiles among MDE patients. Cluster 1 has the highest number of leukocytes, mainly given by the increment in lymphocyte count and the lowest proinflammatory cytokine levels. Cluster 3 displayed the most robust inflammatory pattern, with high levels of TNFα, CX3CL1, IL-12p70, IL-17A, IL-23, and IL-33, associated with the highest level of IL-10, as well as ß-NGF and the lowest level for BDNF. This profile is also associated with the highest absolute number and percentage of circulating monocytes and the lowest absolute number and percentage of circulating lymphocytes, denoting an active inflammatory process. Cluster 2 has some cardinal signs of more acute inflammation, such as elevated levels of CCL2 and increased levels of proinflammatory cytokines such as IL-1ß, IFNγ, and CXCL8. Similarly, the absolute number of monocytes is closer to a HC value, as well as the percentage of lymphocytes, suggesting a possible initiation of the inflammatory process. The study provides new insights into the immune system's role in MDE, paving the ground for replication prospective studies targeting the development of diagnostic and prognostic tools and new therapeutic targets.


Assuntos
Citocinas , Transtorno Depressivo Maior , Imunofenotipagem , Monócitos , Humanos , Feminino , Masculino , Estudos de Casos e Controles , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/sangue , Adulto , Pessoa de Meia-Idade , Citocinas/sangue , Citocinas/imunologia , Monócitos/imunologia , Transtorno Bipolar/imunologia , Transtorno Bipolar/sangue , Inflamação/imunologia , Inflamação/sangue , Antígenos CD/sangue , Antígenos CD/imunologia , Citometria de Fluxo
16.
Transl Psychiatry ; 14(1): 247, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851764

RESUMO

Major depressive disorder (MDD) and bipolar disorder (BD) are highly disabling illnesses defined by different psychopathological, neuroimaging, and cognitive profiles. In the last decades, immune dysregulation has received increasing attention as a central factor in the pathophysiology of these disorders. Several aspects of immune dysregulations have been investigated, including, low-grade inflammation cytokines, chemokines, cell populations, gene expression, and markers of both peripheral and central immune activation. Understanding the distinct immune profiles characterizing the two disorders is indeed of crucial importance for differential diagnosis and the implementation of personalized treatment strategies. In this paper, we reviewed the current literature on the dysregulation of the immune response system focusing our attention on studies using inflammatory markers to discriminate between MDD and BD. High heterogeneity characterized the available literature, reflecting the heterogeneity of the disorders. Common alterations in the immune response system include high pro-inflammatory cytokines such as IL-6 and TNF-α. On the contrary, a greater involvement of chemokines and markers associated with innate immunity has been reported in BD together with dynamic changes in T cells with differentiation defects during childhood which normalize in adulthood, whereas classic mediators of immune responses such as IL-4 and IL-10 are present in MDD together with signs of immune-senescence.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Transtorno Bipolar/imunologia , Transtorno Depressivo Maior/imunologia , Citocinas/imunologia , Mediadores da Inflamação/metabolismo , Biomarcadores , Inflamação/imunologia , Interleucina-6/imunologia
17.
Immun Inflamm Dis ; 12(6): e1307, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38860753

RESUMO

BACKGROUND: The hygiene hypothesis suggests that early life exposure to helminth infections can reduce hypersensitivity in the immune system. OBJECTIVE: The present study aims to evaluate the effects of Toxocara cati (T. cati) somatic products on allergic airway inflammation. METHODS: Between 2018 and 2020, T. cati adult worms were collected from stray cats in Mashhad, Iran (31 out of 186 cats), and their somatic extract was collected. Thirty BALB/c mice were equally divided into three groups, including the OVA group (sensitized and challenged with ovalbumin), the somatic administered group (received somatic extract along with ovalbumin sensitization), and the PBS group (sensitized and challenged with phosphate buffer saline). Bronchoalveolar lavage (BAL) fluid was collected to assess the number of cells, and lung homogenates were prepared for cytokine analysis. Histopathological analysis of the lungs was performed, and inflammatory cells and mucus were detected. Cytokine levels (IL-4, IL-5, IL-10) were measured using enzyme-linked immunosorbent assay (ELISA), and ovalbumin-specific immunoglobulin E (IgE) levels were determined using a capture ELISA. RESULTS: The somatic group significantly decreased regarding the lung pathological changes, including peribronchiolitis, perivasculitis, and eosinophil influx, compared to the group treated with ovalbumin alone. These changes were accompanied by a decrease in proinflammatory cytokines IL-4 and IL-5 and an increase in the anti-inflammatory cytokine IL-10, indicating a shift toward a more balanced immune response. The number of inflammatory cells in the BAL fluid was also significantly reduced in the somatic group, indicating a decrease in inflammation. CONCLUSION: These preclinical findings suggest that in experimental models, T. cati somatic extract exhibits promising potential as a therapeutic agent for mitigating allergic airway inflammation. Its observed effects on immune response modulation and reduction of inflammatory cell infiltration warrant further investigation in clinical studies to assess its efficacy and safety in human patients.


Assuntos
Citocinas , Camundongos Endogâmicos BALB C , Toxocara , Animais , Camundongos , Toxocara/imunologia , Toxocara/efeitos dos fármacos , Citocinas/metabolismo , Citocinas/imunologia , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Ovalbumina/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/parasitologia , Pulmão/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/imunologia , Asma/imunologia , Asma/tratamento farmacológico , Modelos Animais de Doenças , Gatos , Feminino , Toxocaríase/tratamento farmacológico , Toxocaríase/imunologia , Toxocaríase/parasitologia
18.
PLoS Negl Trop Dis ; 18(6): e0012229, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38857253

RESUMO

Leishmania donovani surface glycoprotein 63 (GP63) is a major virulence factor involved in parasite escape and immune evasion. In this study, we generated virus-like particles (VLPs) expressing L. donovani GP63 using the baculovirus expression system. Mice were intramuscularly immunized with GP63-VLPs and challenged with L. donovani promastigotes. GP63-VLP immunization elicited higher levels of L. donovani antigen-specific serum antibodies and enhanced splenic B cell, germinal center B cell, CD4+, and CD8+ T cell responses compared to unimmunized controls. GP63-VLPs inhibited the influx of pro-inflammatory cytokines IFN-γ and IL-6 in the livers, as well as thwarting the development of splenomegaly in immunized mice. Upon L. donovani challenge infection, a drastic reduction in splenic parasite burden was observed in VLP-immunized mice. These results indicate that GP63-VLPs immunization conferred protection against L. donovani challenge infection by inducing humoral and cellular immunity in mice.


Assuntos
Leishmania donovani , Leishmaniose Visceral , Camundongos Endogâmicos BALB C , Vacinas de Partículas Semelhantes a Vírus , Animais , Leishmania donovani/imunologia , Camundongos , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Feminino , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/imunologia , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Vacinas contra Leishmaniose/imunologia , Vacinas contra Leishmaniose/administração & dosagem , Eficácia de Vacinas , Imunidade Celular , Baço/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos B/imunologia , Imunidade Humoral , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/genética , Citocinas/imunologia , Metaloendopeptidases
19.
Viruses ; 16(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38932202

RESUMO

Previous studies from our laboratory and others have established the dendritic cell (DC) as a key target of RSV that drives infection-induced pathology. Analysis of RSV-induced transcriptomic changes in RSV-infected DC revealed metabolic gene signatures suggestive of altered cellular metabolism. Reverse phase protein array (RPPA) data showed significantly increased PARP1 phosphorylation in RSV-infected DC. Real-time cell metabolic analysis demonstrated increased glycolysis in PARP1-/- DC after RSV infection, confirming a role for PARP1 in regulating DC metabolism. Our data show that enzymatic inhibition or genomic ablation of PARP1 resulted in increased ifnb1, il12, and il27 in RSV-infected DC which, together, promote a more appropriate anti-viral environment. PARP1-/- mice and PARP1-inhibitor-treated mice were protected against RSV-induced immunopathology including airway inflammation, Th2 cytokine production, and mucus hypersecretion. However, delayed treatment with PARP1 inhibitor in RSV-infected mice provided only partial protection, suggesting that PARP1 is most important during the earlier innate immune stage of RSV infection.


Assuntos
Células Dendríticas , Pulmão , Poli(ADP-Ribose) Polimerase-1 , Infecções por Vírus Respiratório Sincicial , Vírus Sinciciais Respiratórios , Animais , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Camundongos , Células Dendríticas/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Vírus Sinciciais Respiratórios/imunologia , Camundongos Knockout , Citocinas/metabolismo , Citocinas/imunologia , Imunidade Inata , Feminino
20.
Int Immunopharmacol ; 137: 112360, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38852524

RESUMO

Sarcoidosis is a systemic granulomatous disease characterized by non-caseating epithelioid cell granulomas. One of its immunological hallmarks is the differentiation of CD4 + naïve T cells into Th1/Th17 cells, accompanied by the release of numerous pro-inflammatory cytokines. The TL1A/DR3 signaling pathway plays a crucial role in activating effector lymphocytes, thereby triggering pro-inflammatory responses. The primary aim of this investigation was to scrutinize the impact of anti-TL1A monoclonal antibody on the dysregulation of Th1/Th17 cells and granuloma formation in sarcoidosis. Initially, the abnormal activation of the TL1A/DR3 signaling pathway in pulmonary tissues of sarcoidosis patients was confirmed using qPCR and immunohistochemistry techniques. Subsequently, employing a murine model of sarcoidosis, the inhibitory effects of anti-TL1A monoclonal antibody on the TL1A/DR3 signaling pathway in sarcoidosis were investigated through qPCR, immunohistochemistry, and Western blot experiments. The influence of anti-TL1A monoclonal antibody on granulomas was assessed through HE staining, while their effects on sarcoidosis Th1/Th17 cells and associated cytokine mRNA levels were evaluated using flow cytometry and qPCR, respectively. Immunofluorescence and Western blot experiments corroborated the inhibitory effects of anti-TL1A monoclonal antibody on the aberrant activation of the PI3K/AKT signaling pathway in sarcoidosis. The findings of this study indicate that the TL1A/DR3 signaling pathway is excessively activated in sarcoidosis. Anti-TL1A monoclonal antibody effectively inhibit this abnormal activation in sarcoidosis, thereby alleviating the dysregulation of Th1/Th17 cells and reducing the formation of pulmonary granulomas. This effect may be associated with the inhibition of the downstream PI3K/AKT signaling pathway. Anti-TL1A monoclonal antibody hold promise as a potential novel therapeutic intervention for sarcoidosis.


Assuntos
Anticorpos Monoclonais , Granuloma , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Sarcoidose , Transdução de Sinais , Células Th1 , Células Th17 , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Animais , Células Th1/imunologia , Células Th17/imunologia , Transdução de Sinais/efeitos dos fármacos , Humanos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/imunologia , Granuloma/imunologia , Granuloma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/imunologia , Feminino , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia , Masculino , Sarcoidose/imunologia , Sarcoidose/tratamento farmacológico , Camundongos , Adulto , Pessoa de Meia-Idade , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/imunologia , Pulmão/imunologia , Pulmão/patologia , Citocinas/metabolismo , Citocinas/imunologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
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