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1.
Eur J Endocrinol ; 183(5): R133-R147, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32755992

RESUMO

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Imunidade Inata/imunologia , Imunocompetência/imunologia , Pulmão/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Vitamina D/imunologia , Peptídeos Catiônicos Antimicrobianos/imunologia , Autofagia/imunologia , Betacoronavirus , Defensinas/imunologia , Humanos , Pandemias , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Vitamina D/análogos & derivados
2.
PLoS One ; 15(7): e0236744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730309

RESUMO

Repeated exposures to environmental allergens in susceptible individuals drive the development of type 2 inflammatory conditions such as asthma, which have been traditionally considered to be mainly mediated by Th2 cells. However, emerging evidence suggest that a new innate cell type, group 2 innate lymphoid cells (ILC2), plays a central role in initiating and amplifying a type 2 response, even in the absence of adaptive immunity. At present, the regulatory mechanisms for controlling ILC2 activation remain poorly understood. Here we report that respiratory delivery of immunogenic extracellular RNA (exRNAs) derived from RNA- and DNA-virus infected cells, was able to activate a protective response against acute type 2 lung immunopathology and airway hyperresponsiveness (AHR) induced by IL-33 and a fungal allergen, A. flavus, in mice. Mechanistically, we found that the innate immune responses triggered by exRNAs had a potent suppressive effect in vivo on the proliferation and function of ILC2 without the involvement of adaptive immunity. We further provided the loss-of-function genetic evidence that the TLR3- and MAVS-mediated signaling axis is essential for the inhibitory effects of exRNAs in mouse lungs. Thus, our results indicate that the host detection of extracellular immunostimulatory RNAs generated during respiratory viral infections have an important function in the regulation of ILC2-driven acute lung inflammation.


Assuntos
Armadilhas Extracelulares/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Pneumonia/imunologia , RNA/imunologia , Hipersensibilidade Respiratória/imunologia , Imunidade Adaptativa , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Citocinas/metabolismo , Armadilhas Extracelulares/metabolismo , Interleucina-33/imunologia , Interleucina-33/metabolismo , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/metabolismo , Pneumonia/patologia , RNA/metabolismo , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Transdução de Sinais , Células Th2/imunologia , Células Th2/metabolismo , Receptor 3 Toll-Like/fisiologia
3.
Exp Parasitol ; 216: 107944, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32619431

RESUMO

Evaluation of the murine isotype antibodies is essential in subunit vaccine development because inbred mouse strains with diverse genetic backgrounds respond different to recombinant proteins. In this regard, the main goal of this study was to measuring and comparing the profile of IgG isotype responses in C57BL/6 mice. For this purpose, the extracellular region of plasmodium vivax thrombospondin-related adhesive protein (PvTRAP) gene was expressed in Escherichia coli Rosetta (DE3)-pET23a. Then, the recombinant PvTRAP alone or emulsified with Freund's complete adjuvant were applied for immunization of the C57BL/6 mice. The role of antibodies and cellular immune responses induced by recombinant PvTRAP were evaluated. The results showed the level of anti-rPvTRAP IgG2c was significantly higher than IgG2a in the groups that received rPvTRAP alone (mean OD490 = 0.798 ± 0.12 and 0.39 ± 0.1, respectively) and emulsified with CFA/IFA (mean OD490 = 1.48 ± 0.07 and 0.605 ± 0.13, respectively; P < 0.05, independent sample t-test). Additionally, the immunized mice with rPvTRAP and rPvTRAP + CFA/IFA had an intermediate-avidity IgG2a antibody but high-avidity IgG2c antibody as well as the mean of serum antibody titers results exhibited that in both rPvTRAP and rPvTRAP + CFA/IFA mouse groups, IgG2a end-point titer (1:3200 and 1:25,600, respectively) was noteworthy lower than IgG2c (1:25,600 and 1:102,400, respectively). Moreover, the results revealed the eliciting significant levels of IFN-γ (P < 0.05, independent sample t-test) and no detectable level of IL-4 in the mouse groups received rPvTRAP alone and emulsified with CFA/IFA as compared to the mouse control groups. In general, our results showed that for correctly interpreting of Th1 immune responses in C57BL/6 mouse strain it is critical to measure IgG2c instead of IgG2a along with IFN-γ.


Assuntos
Imunoglobulina G/sangue , Plasmodium vivax/imunologia , Proteínas de Protozoários/imunologia , Vacinas Protozoárias/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Afinidade de Anticorpos , Dicroísmo Circular , Feminino , Imunofluorescência , Imunoglobulina G/classificação , Interferon gama/análise , Interleucina-4/análise , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Vacinas de Subunidades/imunologia , Vacinas Sintéticas/imunologia
4.
PLoS Comput Biol ; 16(7): e1008051, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730250

RESUMO

In the animal kingdom, various forms of swarming enable groups of autonomous individuals to transform uncertain information into unified decisions which are probabilistically beneficial. Crossing scales from individual to group decisions requires dynamically accumulating signals among individuals. In striking parallel, the mammalian immune system is also a group of decentralized autonomous units (i.e. cells) which collectively navigate uncertainty with the help of dynamically accumulating signals (i.e. cytokines). Therefore, we apply techniques of understanding swarm behavior to a decision-making problem in the mammalian immune system, namely effector choice among CD4+ T helper (Th) cells. We find that incorporating dynamic cytokine signaling into a simple model of Th differentiation comprehensively explains divergent observations of this process. The plasticity and heterogeneity of individual Th cells, the tunable mixtures of effector types that can be generated in vitro, and the polarized yet updateable group effector commitment often observed in vivo are all explained by the same set of underlying molecular rules. These rules reveal that Th cells harness dynamic cytokine signaling to implement a system of quorum sensing. Quorum sensing, in turn, may confer adaptive advantages on the mammalian immune system, especially during coinfection and during coevolution with manipulative parasites. This highlights a new way of understanding the mammalian immune system as a cellular swarm, and it underscores the power of collectives throughout nature.


Assuntos
Percepção de Quorum , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Diferenciação Celular , Citocinas/imunologia , Tomada de Decisões , Humanos , Sistema Imunitário , Interferon gama/imunologia , Ativação Linfocitária , Modelos Teóricos , Probabilidade , Transdução de Sinais , Processos Estocásticos , Linfócitos T Auxiliares-Indutores/citologia , Células Th1/citologia , Células Th1/imunologia , Células Th2/citologia , Células Th2/imunologia
5.
Int Arch Allergy Immunol ; 181(8): 624-628, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544911

RESUMO

A vaccine to protect against COVID-19 is urgently needed. Such a vaccine should efficiently induce high-affinity neutralizing antibodies which neutralize SARS-CoV-2, the cause of COVID-19. However, there is a concern regarding both vaccine-induced eosinophilic lung disease and eosinophil-associated Th2 immunopotentiation following infection after vaccination. Here, we review the anticipated characteristics of a COVID-19 vaccine to avoid vaccine-associated eosinophil immunopathology.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Eosinófilos/fisiologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Células Th2/imunologia , Vacinação/efeitos adversos , Vacinas Virais/efeitos adversos , Anticorpos Neutralizantes/biossíntese , Infecções por Coronavirus/imunologia , Humanos , Vacinas Virais/imunologia
6.
PLoS One ; 15(6): e0233563, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497050

RESUMO

Activation of the steroidogenic enzyme CYP11A1 was shown to be necessary for the development of peanut-induced intestinal anaphylaxis and IL-13 production in allergic mice. We determined if levels of CYP11A1 in peripheral blood T cells from peanut-allergic (PA) children compared to non-allergic controls were increased and if levels correlated to IL-13 production and oral challenge outcomes to peanut. CYP11A1 mRNA and protein levels were significantly increased in activated CD4+ T cells from PA patients. In parallel, IL-13 production was significantly increased; IFNγ levels were not different between groups. There were significant correlations between expression levels of CYP11A1 mRNA and levels of IL13 mRNA and protein, levels of serum IgE anti-Ara h 2 and to outcomes of peanut challenge. The importance of CYP11A1 on cytokine production was tested using a CYP11A1 CRISPR/Cas9 KO plasmid or an inhibitor of enzymatic CYP11A1 activity. Inhibition of CYP11A1 activation in patient cells treated with the inhibitor, aminoglutethimide, or CD4+ T cell line transfected with the CYP11A1 KO plasmid resulted in reduced IL-13 production. These data suggest that the CYP11A1-CD4+Tcell-IL-13 axis in activated CD4+ T cells from PA children is associated with development of PA reactions. CYP11A1 may represent a novel target for therapeutic intervention in PA children.


Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Interleucina-13/biossíntese , Hipersensibilidade a Amendoim/imunologia , Células Th2/imunologia , Adolescente , Aminoglutetimida/farmacologia , Linhagem Celular , Criança , Pré-Escolar , Enzima de Clivagem da Cadeia Lateral do Colesterol/antagonistas & inibidores , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Feminino , Técnicas de Inativação de Genes , Humanos , Ativação Linfocitária , Masculino , Hipersensibilidade a Amendoim/sangue , RNA Mensageiro/genética , Transfecção , Adulto Jovem
7.
Clin Immunol ; 217: 108487, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32479986

RESUMO

Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Doenças do Complexo Imune/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Células Th2/imunologia , Vasculite/imunologia , Idoso , Anticorpos Antivirais/biossíntese , Complexo Antígeno-Anticorpo/biossíntese , Betacoronavirus/imunologia , Vasos Sanguíneos/imunologia , Vasos Sanguíneos/patologia , Vasos Sanguíneos/virologia , Complemento C3/biossíntese , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Progressão da Doença , Células Endoteliais/imunologia , Células Endoteliais/patologia , Células Endoteliais/virologia , Humanos , Doenças do Complexo Imune/complicações , Doenças do Complexo Imune/virologia , Imunidade Humoral , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Interleucina-6/biossíntese , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/virologia , Células Th2/patologia , Células Th2/virologia , Vasculite/complicações , Vasculite/virologia
9.
PLoS Negl Trop Dis ; 14(6): e0008069, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32498074

RESUMO

Africa is the second most populous continent and has perennial health challenges. Of the estimated 181 million school aged children in sub-Saharan Africa (SSA), nearly half suffer from ascariasis, trichuriasis, or a combination of these infections. Coupled with these is the problem of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection, which is a leading cause of death in the region. Compared to the effect of the human immunodeficiency virus on the development of TB, the effect of chronic helminth infections is a neglected area of research, yet helminth infections are as ubiquitous as they are varied and may potentially have profound effects upon host immunity, particularly as it relates to TB infection, diagnosis, and vaccination. Protection against active TB is known to require a clearly delineated T-helper type 1 (Th1) response, while helminths induce a strong opposing Th2 and immune-regulatory host response. This Review highlights the potential challenges of helminth-TB co-infection in Africa and the need for further research.


Assuntos
Ascaríase/epidemiologia , Coinfecção/epidemiologia , Tricuríase/epidemiologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/complicações , Tuberculose/epidemiologia , Adolescente , África/epidemiologia , Ascaríase/complicações , Ascaríase/imunologia , Criança , Pré-Escolar , Coinfecção/imunologia , Coinfecção/prevenção & controle , Feminino , Humanos , Lactente , Masculino , Prevalência , Células Th1/imunologia , Células Th2/imunologia , Tricuríase/complicações , Tricuríase/imunologia , Tuberculose/imunologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/administração & dosagem
12.
PLoS One ; 15(5): e0233047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392269

RESUMO

Fruits have been widely considered as the default "health foods" because they contain numerous vitamins and minerals needed to sustain human health. Fermentation strategies have been utilized to enhance the nutritive and flavor features of healthy and readily consumable fruit products while extending their shelf lives. A traditional fermented multi-fruit beverage was made from five fruits including kiwi, guava, papaya, pineapple, and grape fermented by Saccharomyces cerevisiae along with lactic acid bacteria and acetic acid bacteria. The immunomodulatory properties of the fermented multi-fruit beverage, in vivo nonspecific and ovalbumin (OVA)-specific immune response experiments using female BALB/c mice were performed. Administration of the fermented multi-fruit beverage reduced the calorie intake, thus resulting in a less weight gain in mice compared to the water (placebo)-fed mice. In the nonspecific immune study model, the fermented multi-fruit beverage enhanced phagocytosis and T cell proliferation but did not affect B cell proliferation and immunoglobulin G (IgG) production. Analysis of cytokine secretion profile also revealed that the fermented multi-fruit beverage enhanced proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and T helper (Th)1-related cytokine interferon (IFN)-γ production, thus creating an immunostimulatory effect. Nonetheless, in the specific immune study model, the results showed that the fermented multi-fruit beverage decreased the production of proinflammatory cytokines IL-6 and TNF-α production in OVA-immunized mice. Moreover, it also caused a decrease in the production of anti-OVA IgG1, which was accompanied by a decrease in Th2-related cytokines IL-4 and IL-5 production and an increase in Th1-related cytokine IFN-γ production, indicating that it may have the potential to shift the immune system from the allergen-specific Th2 responses toward Th1-type responses. The results indicate that fermented multi-fruit beverage has the potential to modulate immune responses both in a nonspecific and specific manners.


Assuntos
Citocinas/metabolismo , Alimentos e Bebidas Fermentados/microbiologia , Frutas/imunologia , Ovalbumina/administração & dosagem , Linfócitos T/metabolismo , Acetobacteraceae/fisiologia , Administração Oral , Animais , Peso Corporal , Feminino , Imunoglobulina G/metabolismo , Lactobacillales/fisiologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Fagocitose , Saccharomyces cerevisiae/fisiologia , Células Th1/imunologia , Células Th2/imunologia , Vacinação
13.
Nat Commun ; 11(1): 2550, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439962

RESUMO

The inherent molecular complexity of human pathogens requires that mammals evolved an adaptive immune system equipped to handle presentation of non-conventional MHC ligands derived from disease-causing agents, such as HIV-1 envelope (Env) glycoprotein. Here, we report that a CD4+ T cell repertoire recognizes a glycopeptide epitope on gp120 presented by MHCII pathway. This glycopeptide is strongly immunogenic in eliciting glycan-dependent cellular and humoral immune responses. The glycopeptide specific CD4+ T cells display a prominent feature of Th2 and Th17 differentiation and exert high efficacy and potency to help Env trimer humoral immune responses. Glycopeptide-induced CD4+ T cell response prior to Env trimer immunization elicits neutralizing antibody development and production of antibodies facilitating uptake of immunogens by antigen-presenting cells. Our identification of gp120 glycopeptide-induced, T cell-specific immune responses offers a foundation for developing future knowledge-based vaccines that elicit strong and long-lasting protective immune responses against HIV-1 infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Imunidade Humoral/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Neutralizantes/imunologia , Citocinas/metabolismo , Epitopos de Linfócito T/química , Glicopeptídeos/química , Glicopeptídeos/imunologia , Anticorpos Anti-HIV/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Imunidade Celular , Imunização , Camundongos , Polissacarídeos/imunologia , Células Th17/imunologia , Células Th2/imunologia
14.
Proc Natl Acad Sci U S A ; 117(23): 12980-12990, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461368

RESUMO

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin+ and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout (-/-) mice lacking AhR, respectively, in LC and Langerin+ dermal DC and in all CD11c+ cells. These were then tested in an epicutaneous protein (ovalbumin, Ova) sensitization model. Immunofluorescence microscopy and flow cytometry revealed that Langerin-AhR-/- but not CD11c-AhR-/- mice harbored a decreased number of LC with fewer and stunted dendrites in the epidermis as well as a decreased number of LC in skin-draining lymph nodes (LN). Moreover, in the absence of AhR, we detected an enhanced T helper type-2 (Th2) [increased interleukin 5 (IL-5) and interleukin 13 (IL-13)] and T regulatory type-1 (Tr1) (IL-10) response when LN cells were challenged with Ova in vitro, though the number of regulatory T cells (Treg) in the LN remained comparable. Langerin-AhR-/- mice also exhibited increased blood levels of Ova-specific immunoglobulin E (IgE). In conclusion, deletion of AhR in langerin-expressing cells diminishes the number and activation of LC, while enhancing Th2 and Tr1 responses upon epicutaneous protein sensitization.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células de Langerhans/imunologia , Receptores de Hidrocarboneto Arílico/metabolismo , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Administração Cutânea , Animais , Antígenos de Superfície/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Epiderme/imunologia , Epiderme/metabolismo , Técnicas de Inativação de Genes , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Células de Langerhans/metabolismo , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Camundongos , Camundongos Transgênicos , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Receptores de Hidrocarboneto Arílico/genética , Linfócitos T Reguladores/metabolismo , Células Th2/metabolismo
15.
Ecotoxicol Environ Saf ; 199: 110740, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446102

RESUMO

Dibutyl phthalate (DBP) is one of the most ubiquitous phthalate esters found in everyday products, and is receiving increased attention as an immunologic adjuvant. However, information regarding DBP-aggravated allergic asthma is still limited. This study used a mouse model sensitized with ovalbumin (OVA) to determine any adverse effects of DBP on allergic asthma. Our results reveal that allergic asthmatic mice exposed to DBP for an extended period had a significant increase in inflammatory cell infiltration; a significant increase in levels of serum immunoglobulin and T helper 2 cell (Th2) and T helper 17 cell (Th17) cytokines in lung tissue; and significant changes in lung histology and AHR, all of which are typical asthmatic symptoms. The levels of oxidative stress and levels of the neuropeptide, calcitonin gene related peptide (CGRP), were also elevated after DBP exposure. Interestingly, blocking oxidative stress by administering melatonin (MT) not only reduced oxidative stress and CGRP levels, but also ameliorated the asthmatic symptoms. Collectively, these results show that DBP exacerbates asthma-like pathologies by increasing the expression of CGRP mediated by oxidative stress.


Assuntos
Asma/induzido quimicamente , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dibutilftalato/toxicidade , Poluentes Ambientais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Asma/imunologia , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
16.
Exp Parasitol ; 215: 107917, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446699

RESUMO

Cystic echinococcosis (CE) is a worldwide hazardous zoonotic parasitosis caused by Echinococcus granulosus. CE development involves complex immunological mechanisms, including participation of multiple immune cells and effector molecules. Myeloid-derived suppressor cells (MDSCs) are known to be involved in chronic and acute inflammatory conditions. In this study, we aimed to characterize the immune function of MDSCs in CE to improve the understanding, prevention and treatment of CE. Our results indicated that MDSCs overexpressing Ly6C and Ly6G inhibit the formation and activity of T helper 2 cells in a NO-dependent manner during E. granulosus infection.


Assuntos
Equinococose/imunologia , Echinococcus granulosus/imunologia , Células Supressoras Mieloides/imunologia , Células Th2/imunologia , Análise de Variância , Animais , Anticorpos Monoclonais , Arginase/análise , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Citocinas/análise , Feminino , Citometria de Fluxo , Humanos , Ceratolíticos/farmacologia , Camundongos , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/enzimologia , Óxido Nítrico/análise , Espécies Reativas de Oxigênio/análise , Organismos Livres de Patógenos Específicos , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Tretinoína/farmacologia
17.
PLoS Negl Trop Dis ; 14(5): e0008155, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32365058

RESUMO

Plasmodium vivax malaria is a neglected disease, particularly during pregnancy. Severe vivax malaria is associated with inflammatory responses but in pregnancy immune alterations make it uncertain as to what cytokine signatures predominate, and how the type and quantity of blood immune mediators influence delivery outcomes. We measured the plasma concentrations of a set of thirty-one biomarkers, comprising cytokines, chemokines and growth factors, in 987 plasma samples from a cohort of 572 pregnant women from five malaria-endemic tropical countries and related these concentrations to delivery outcomes (birth weight and hemoglobin levels) and malaria infection. Samples were collected at recruitment (first antenatal visit) and at delivery (periphery, cord and placenta). At recruitment, we found that P. vivax-infected pregnant women had higher plasma concentrations of proinflammatory (IL-6, IL-1ß, CCL4, CCL2, CXCL10) and TH1-related cytokines (mainly IL-12) than uninfected women. This biomarker signature was essentially lost at delivery and was not associated with birth weight nor hemoglobin levels. Antiinflammatory cytokines (IL-10) were positively associated with infection and poor delivery outcomes. CCL11 was the only biomarker to show a negative association with P. vivax infection and its concentration at recruitment was positively associated with hemoglobin levels at delivery. Birth weight was negatively associated with peripheral IL-4 levels at delivery. Our multi-biomarker multicenter study is the first comprehensive one to characterize the immunological signature of P. vivax infection in pregnancy thus far. In conclusion, data show that while TH1 and pro-inflammatory responses are dominant during P. vivax infection in pregnancy, antiinflammatory cytokines may compensate excessive inflammation avoiding poor delivery outcomes, and skewness toward a TH2 response may trigger worse delivery outcomes. CCL11, a chemokine largely neglected in the field of malaria, emerges as an important marker of exposure or mediator in this condition.


Assuntos
Citocinas/sangue , Malária Vivax/sangue , Plasmodium vivax/fisiologia , Complicações Parasitárias na Gravidez/sangue , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Interleucina-10/sangue , Interleucina-1beta/sangue , Malária Vivax/imunologia , Malária Vivax/parasitologia , Malária Vivax/fisiopatologia , Masculino , Gravidez , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/fisiopatologia , Resultado da Gravidez , Células Th2/imunologia , Adulto Jovem
18.
Clin Rev Allergy Immunol ; 59(1): 78-88, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32468411

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and abnormal, overactivated innate immunity and "cytokine storms" have been proposed as potential pathological mechanisms for rapid COVID-19 progression. Theoretically, asthmatic patients should have increased susceptibility and severity for SARS-CoV-2 infection due to a deficient antiviral immune response and the tendency for exacerbation elicited by common respiratory viruses. However, existing studies have not shown an expected prevalence of asthmatic individuals among COVID-19 patients. Certain aspects of type 2 immune response, including type 2 cytokines (IL-4, IL-13, etc.) and accumulation of eosinophils, might provide potential protective effects against COVID-19. Furthermore, conventional therapeutics for asthma, including inhaled corticosteroids, allergen immunotherapy (AIT), and anti-IgE monoclonal antibody, might also reduce the risks of asthmatics suffering infection of the virus through alleviating inflammation or enhancing antiviral defense. The interactions between COVID-19 and asthma deserve further attention and clarification.


Assuntos
Asma/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Administração por Inalação , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/imunologia , Asma/terapia , Linfócitos B/imunologia , Betacoronavirus , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Dessensibilização Imunológica , Progressão da Doença , Eosinófilos/imunologia , Humanos , Interleucina-13/imunologia , Interleucina-4/imunologia , Células Matadoras Naturais/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Células T Matadoras Naturais/imunologia , Omalizumab/uso terapêutico , Pandemias , Pneumonia Viral/imunologia , Fatores de Proteção , Fatores de Risco , Células Th2/imunologia
19.
PLoS One ; 15(5): e0226539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413046

RESUMO

A murine model to study the effect of cold-induced stress (CIS) on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Previous results in the lab show that CIS increases the intensity of chlamydia genital infection, but little is known about the effects and mechanisms of CIS on the differentiation and activities of CD4+ T cell subpopulations and bone marrow-derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines are not well defined. In this study, we examined whether CIS modulates the expressions of beta-adrenergic receptor (ß-AR), transcription factors, hallmark cytokines of Th1 and Th2, and differentiation of BMDCs during C. muridarum genital infection in the murine model. Our results show that the mRNA level of the beta2-adrenergic receptor (ß2-AR) compared to ß1-AR and ß3-AR was high in the mixed populations of CD4+ T cells and BMDCs. Furthermore, we observed decreased expression of T-bet, low level of Interferon-gamma (IFN-γ) production, increased expression of GATA-3, and Interleukin-4 (IL-4) production in CD4+ T cells of stressed mice. Exposure of BMDCs to Fenoterol, ß2-AR agonist, or ICI118,551, ß2-AR antagonist, revealed significant ß2-AR stimulation or inhibition, respectively, in stressed mice. Moreover, co-culturing of mature BMDCs and naïve CD4+ T cells increased the production of IL-4, IL-10, L-17, and IL-23 cytokines, suggesting that stimulation of ß2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that CIS promotes the switching from a Th1 to Th2 cytokine environment. This was evidenced in the murine stress model by the overexpression of GATA-3 concurrent with elevated IL-4 production, reduced T-bet expression, and IFN-γ secretion.


Assuntos
Infecções por Chlamydia/imunologia , Resposta ao Choque Frio , Células Th1/imunologia , Células Th2/imunologia , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Células Cultivadas , Chlamydia muridarum , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Fenoterol/farmacologia , Interferon gama/genética , Interferon gama/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Propanolaminas/farmacologia , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Cell Prolif ; 53(6): e12827, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32406154

RESUMO

OBJECTIVES: Previously, we found that by regulating T helper (Th) cell polarization, calcitriol intervention inhibited lipopolysaccharide (LPS)-induced alveolar bone loss in an animal periodontitis model, but the underlying cellular events remain unknown. MATERIALS AND METHODS: In this study, mouse Th cells were incubated in an inflammatory environment in the presence of dendritic cells (DCs) and LPS. Then, the potential of the Th cells to undergo Th2/Th17 polarization, the RANKL expression of the polarized Th cells and the subsequent influences of the polarized Th cells on RAW264.7 cell osteoclastogenesis in response to calcitriol administration were assessed. Finally, the effects of calcitriol on antigen presentation by DCs during these cellular events were evaluated. RESULTS: In response to calcitriol administration, Th cells in an inflammatory environment exhibited an enhanced potential for Th2 polarization along with a decreased potential for Th17 polarization. In addition, RANKL expression in Th17-polarized cells was largely inhibited. Furthermore, inflammation-induced osteoclastogenesis in RAW264.7 cells was suppressed following coculture with calcitriol-treated Th cells. During these cellular events, increased expression of Th2 promoters (such as OX-40L and CCL17) and decreased expression of Th17 promoters (such as IL-23 and IL-6) were found in DCs. CONCLUSIONS: Calcitriol can inhibit osteoclastogenesis in an inflammatory environment by changing the proportion and function of Th cell subsets. Our findings suggest that calcitriol may be an effective therapeutic agent for treating periodontitis.


Assuntos
Calcitriol/farmacologia , Osteoclastos/citologia , Osteogênese/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Animais , Células Cultivadas , Células Dendríticas/imunologia , Inflamação , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Fenótipo , Regiões Promotoras Genéticas , Ligante RANK/metabolismo , Células RAW 264.7 , Células Th17/imunologia , Células Th2/imunologia
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