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2.
Scand J Immunol ; 91(3): e12855, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31793015

RESUMO

Asthma is a clinical syndrome characterized by chronic airway inflammation. There is mounting evidence on the role of microbiota in the development of asthma. This review focuses on the role of microbiota in maintaining the integrity of the epithelia and their role in regulating the immune response. The review compiles data from multiple studies on the role of microbiota in the innate immune response and the development and differentiation of CD4+ T cells, a major component of the adaptive arm of the immune response. As a result of dysbiosis, invariant natural killer T cells may induce T helper 2 cell differentiation and immunoglobulin E isotype switching through the release of interleukin-4 and interleukin-13. Furthermore, degradation of immunoglobulin A antibodies, increased circulating mast cells and basophils, and inflammation are among other mechanisms by which dysbiosis can induce or exacerbate asthma. After explaining the underlying mechanisms, the review derives conclusions from studies that investigate dysbiosis in infancy and the development of asthma later in life. The review also includes studies that investigate asthmatic mothers and the development of asthma in children and the role of dysbiosis in that regard. Finally, the review explains the statistical relationship between eczema and asthma through multiple studies that investigate the role of dysbiosis in both atopic states. This review provides insight into the role of dysbiosis in asthma, and an understanding that is required to establish clinical trials which aim to modulate the gut microbiota as a means of preventing and treating asthma.


Assuntos
Asma/etiologia , Microbioma Gastrointestinal , Hipersensibilidade/etiologia , Fatores Etários , Animais , Suscetibilidade a Doenças , Disbiose , Microbioma Gastrointestinal/imunologia , Humanos , Hipersensibilidade Imediata/etiologia , Imunidade nas Mucosas , Imunomodulação , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia
3.
Immunology ; 159(1): 52-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31777063

RESUMO

Immunology research in the last 50 years has made huge progress in understanding the mechanisms of anti-bacterial defense of deep, normally sterile, tissues such as blood, spleen and peripheral lymph nodes. In the intestine, with its dense commensal microbiota, it seems rare that this knowledge can be simply translated. Here we put forward the idea that perhaps it is not always the theory of immunology that is lacking to explain mucosal immunity, but rather that we have overlooked crucial parts of the mucosal immunological language required for its translation: namely intestinal and bacterial physiology. We will try to explain this in the context of intestinal secretory antibodies (mainly secretory IgA), which have been described to prevent, to alter, to not affect, or to promote colonization of the intestine and gut-draining lymphoid tissues, and where effector mechanisms have remained elusive. In fact, these apparently contradictory outcomes can be generated by combining the basic premises of bacterial agglutination with an understanding of bacterial growth (i.e. secretory IgA-driven enchained growth), fluid handling and bacterial competition in the gut lumen.


Assuntos
Bactérias/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas , Imunoglobulina A Secretora/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Imunoglobulina A Secretora/metabolismo , Dinâmica Populacional , Transdução de Sinais
4.
Immunology ; 159(1): 1-3, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31777065

RESUMO

The field of mucosal immunology has, for the last 10 years, been largely dominated by advances in our understanding of the commensal microbiota. Developments of novel experimental methodologies and analysis techniques have provided unparalleled insight into the profound impact the microbiota has on the development and function of the immune system. In this cross-journal review series published in Immunology and Clinical and Experimental Immunology, we aim to summarize the current state of research concerning the interplay between the microbiota and mucosal immunity. In addition, the series examines how the increased understanding of the microbiota is changing the nature of immunological research, both in the laboratory and in the clinic.


Assuntos
Microbioma Gastrointestinal/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade nas Mucosas , Animais , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia
5.
Immunology ; 159(1): 39-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31777064

RESUMO

Immunity is shaped by commensal microbiota. From early life onwards, microbes colonize mucosal surfaces of the body and thereby trigger the establishment of immune homeostasis and defense mechanisms. Recent evidence reveals that the family of innate lymphoid cells (ILCs), which are mainly located in mucosal tissues, are essential in the maintenance of barrier functions as well as in the initiation of an appropriate immune response upon pathogenic infection. In this review, we summarize recent insights on the functional interaction of microbiota and ILCs at steady-state and throughout life. Furthermore, we will discuss the interplay of ILCs and the microbiota in mucosal infections focusing on intestinal immunity.


Assuntos
Bactérias/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Linfócitos/imunologia , Linfócitos/microbiologia , Fatores Etários , Envelhecimento/imunologia , Animais , Bactérias/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Mucosa Intestinal/metabolismo , Linfócitos/metabolismo , Neoplasias/imunologia , Neoplasias/microbiologia , Transdução de Sinais
6.
Immunology ; 159(1): 26-38, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31777068

RESUMO

Mucosal tissues contain distinct microbial communities that differ drastically depending on the barrier site, and as such, mucosal immune responses have evolved to be tailored specifically for their location. Whether protective or regulatory immune responses against invading pathogens or the commensal microbiota occur is controlled by local mononuclear phagocytes (MNPs). Comprising macrophages and dendritic cells (DCs), the functions of these cells are highly dependent on the local environment. For example, the intestine contains the greatest bacterial load of any site in the body, and hence, intestinal MNPs are hyporesponsive to bacterial stimulation. This is thought to be one of the major mechanisms by which harmful immune responses directed against the trillions of harmless bacteria that line the gut lumen are avoided. Regulation of MNP function by the microbiota has been characterized in the most depth in the intestine but there are several mucosal sites that also contain their own microbiota. In this review, we present an overview of how MNP function is regulated by the microbiota at mucosal sites, highlighting recent novel pathways by which this occurs in the intestine, and new studies elucidating these interactions at mucosal sites that have been characterized in less depth, including the urogenital tract.


Assuntos
Imunidade nas Mucosas , Microbiota/imunologia , Sistema Fagocitário Mononuclear/imunologia , Membrana Mucosa/microbiologia , Simbiose/imunologia , Animais , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Tolerância Imunológica , Intestinos/imunologia , Intestinos/microbiologia , Pulmão/microbiologia , Modelos Animais , Boca/imunologia , Boca/microbiologia , Membrana Mucosa/imunologia , Sistema Urogenital/imunologia , Sistema Urogenital/microbiologia
7.
Immunology ; 159(1): 15-25, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31777069

RESUMO

The intricate host-microbial interaction and the overwhelming complexity of the mucosal immune system in the adult host raise the question of how this system is initially established. Here, we propose the implementation of the concept of the 'postnatal window of opportunity' into the model of a 'layered immunity' to explain how the newborn's mucosal immune system matures and how host-microbial immune homeostasis is established after birth. We outline the concept of a timed succession of non-redundant phases during postnatal immune development and discuss the possible influence of external factors and conditions.


Assuntos
Microbioma Gastrointestinal/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Sistema Imunitário/crescimento & desenvolvimento , Imunidade nas Mucosas , Mucosa Intestinal/microbiologia , Imunidade Adaptativa/imunologia , Animais , Homeostase/imunologia , Humanos , Imunidade Inata/imunologia , Recém-Nascido , Mucosa Intestinal/imunologia , Modelos Animais , Fatores de Tempo
8.
Adv Exp Med Biol ; 1197: 1-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732930

RESUMO

The 1st International Conference on Oral Mucosal Immunity and the Microbiome (OMIM) took place at the Avra Imperial Hotel, Chania, Crete, Greece, between 26th and 30th September 2018, under the auspices of the Aegean Conferences. This was the first Aegean Conference of its kind in thematic oral research, and a unique blend of immunological and microbiological perspectives, which attracted leading scientists from around the world to discuss the latest advances in the field. The Conference was divided into eight sessions that spanned across 4 days and included the following topics: (a) mucosal barrier immunity; (b) host response and inflammation; (c) microbiome in homeostasis and dysbiosis; (d) fungal and viral pathogenesis; (e) oral microbiome and proteome; (f) microbial virulence and biofilms; (g) microbiome, cancer, and systemic disease; and (h) microbiota and inflammation. There was substantial thematic overlap among all sessions, which promoted constant involvement of the participating scientists. An important hallmark was the active debate between oral microbiologists and oral immunologists, who explored new ideas and potential research collaborations, a crucial aspect for bridging our understanding of oral diseases in the context of the whole body. Key findings are highlighted and thematically presented in the following sections.


Assuntos
Imunidade nas Mucosas , Microbiota , Mucosa Bucal , Disbiose , Grécia , Humanos , Inflamação , Mucosa Bucal/microbiologia
9.
Adv Exp Med Biol ; 1197: 11-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732931

RESUMO

The long-standing dogma that immunological memory is the exclusive prerogative of the adaptive immune system has been challenged by emerging evidence that innate immunity can also maintain memory of past events. Such immunological imprinting takes two forms, trained innate immunity and tolerance. Trained immunity involves metabolic and epigenetic adaptations in innate immune cells and their progenitors in the bone marrow upon exposure to certain microbial and/or inflammatory stimuli so that the "trained" cells would be poised to respond much faster and stronger to a subsequent challenge (e.g., a new infection that is not necessarily the same as the earlier one). Conversely, tolerance leads to attenuated immune responses to secondary stimuli. This review focuses on trained immunity and discusses evidence for its existence from lower organisms to humans, its mechanistic underpinnings, and its translational ramifications. Although trained immunity can be considered as an evolutionarily conserved beneficial response against reinfections, in the setting of modern societies with high prevalence of chronic mucosal and systemic inflammatory diseases, trained immunity could also promote maladaptive immune responses that aggravate pathology. Thus, depending on context, innate immune memory could be therapeutically manipulated using defined agonists to either promote innate immune responses (particularly useful for the treatment of infections or chemotherapy-induced myelosuppression) or suppress excessive inflammation in inflammatory and autoimmune diseases.


Assuntos
Imunidade Inata , Imunidade nas Mucosas , Memória Imunológica , Humanos , Imunidade Inata/imunologia , Imunidade nas Mucosas/imunologia , Inflamação
10.
Vet Microbiol ; 237: 108401, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31585639

RESUMO

Influenza results in significant economic loss in the swine industry each year. A broadly protective swine influenza vaccine would have the dual benefit of protecting pigs from influenza A viruses (IAVs) and limiting their possible zoonotic transmission to humans. In this study, we developed polyanhydride nanoparticles-based swine influenza vaccine (KAg + CpG-nanovaccine) co-encapsulating inacticated/killed soluble antigen (KAg) and Toll-like receptor (TLR)-9 agonist (CpG-ODN). The immunogenicity and protective efficacy of KAg + CpG-nanovaccine was compared with KAg vaccine containing five-times greater quantity of antigens following heterologous virus challenge. Prime-boost intranasally delivered KAg + CpG-nanovaccine induced significantly higher levels of cross-reactive antigen-specific IgA antibody responses in the nasal cavity, greater lymphoproliferative response in peripheral blood mononuclear cells (PBMCs), and higher IFN-γ secretion during antigen-induced recall responses of PBMCs and tracheobronchial lymph nodes cells compared to those immunized with KAg alone. Importantly, KAg + CpG-nanovaccine provided better protective efficacy through a significant reduction in influenza-induced fever, 16-fold reduction of nasal virus shedding and 80-fold reduction in lung virus titers compared to those immunized with soluble KAg. Our results indicated that CpG-ODN-adjuvanted polyanhydride nanovaccine can induce higher mucosal antibody and cellular immune responses in pigs; and provide better protection as compared with intranasally delivered soluble KAg.


Assuntos
Vacinas contra Influenza/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/prevenção & controle , Adjuvantes Imunológicos , Administração Intranasal , Animais , Anticorpos Antivirais , Antígenos Virais/imunologia , Feminino , Imunidade nas Mucosas , Imunoglobulina A/imunologia , Interferon gama/metabolismo , Leucócitos Mononucleares , Masculino , Nanoestruturas , Oligodesoxirribonucleotídeos/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Polianidridos , Suínos , Vacinas de Produtos Inativados/imunologia
11.
Vet Clin North Am Food Anim Pract ; 35(3): 431-451, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590896

RESUMO

This article discusses key concepts important for mucosal immunity. The mucosa is the largest immune organ of the body. The mucosal barrier (the tight junctions and the "kill zone") along with the mucosa epithelial cells maintaining an anti-inflammatory state are essential for the mucosal firewall. The microbiome (the microorganisms that are in the gastrointestinal, respiratory, and reproductive tract) is essential for immune development, homeostasis, immune response, and maximizing animal productivity. Mucosal vaccination provides an opportunity to protect animals from most infectious diseases because oral, gastrointestinal, respiratory, and reproductive mucosa are the main portals of entry for infectious disease.


Assuntos
Bovinos/imunologia , Imunidade nas Mucosas/imunologia , Animais , Feminino , Imunidade Celular , Imunidade Humoral
12.
Vet Clin North Am Food Anim Pract ; 35(3): 485-505, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590899

RESUMO

New insights into the host-microbiota relationship have recently emerged with the advancement of molecular technologies such as next-generation sequencing. This article presents the current knowledge regarding the interaction between bacteria and the immune system of the gut, the uterus, and the mammary gland of cattle.


Assuntos
Bovinos/imunologia , Bovinos/microbiologia , Sistema Imunitário/microbiologia , Microbiota/imunologia , Animais , Feminino , Imunidade nas Mucosas/imunologia
13.
Fish Shellfish Immunol ; 94: 711-722, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31574297

RESUMO

An 8-week growth trial was conducted to investigate the effects of replacing dietary fishmeal with a plant protein blend on the growth performance, mucosal barrier integrity and the related regulation mechanism in Amur Sturgeon (Acipenser schrenckii) with initial weight of 87.48 g. Three isonitrogenous and isoenergetic diets were prepared. A basal diet containing 540 g/kg fishmeal (P0), whereas the other two diets were formulated by replacing 50% and 100% of FM with plant protein blend (soybean protein concentrate and cottonseed protein concentrate), and named as P50 and P100, respectively. Although essential amino acids, fatty acids, and available phosphorus had been balanced according to the nutrient requirement of sturgeon, compared with the fish of P0 and P50, the full plant protein diet (P100) significantly reduced growth performance and survival, and accompanied with serious spiral valve intestinal (SVI) damage. The increased tissue necrosis and failed responses in anti-oxidation, programming apoptosis, autophagy and cell proliferation system were regulated by inhibiting ERK1 phosphorylation, which indicated that SVI hypoimmunity and functional degradation were the main reasons for the high mortality and low utilization ability of plant protein in Amur sturgeon.


Assuntos
Peixes/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Proteínas de Vegetais Comestíveis/imunologia , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dieta/veterinária
14.
World J Gastroenterol ; 25(36): 5469-5482, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576093

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gas-troenterological diseases characterized by abnormal visceral sensitivity and low-grade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1ß, IL-6, and others) and express T cell immuno-globulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM: To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS: An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1ß and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrow-derived dendritic cells by in vitro experiments. RESULTS: The secretion of proinflammatory cytokines (IL-1ß and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1ß and IL-6) were significantly reduced after the intervention with probiotic C. butyricum. The amount and function of LPDCs and the TIM3 on the surface of the LPDCs were decreased with the alleviation of the intestinal inflammatory response. CONCLUSION: The results suggest that C. butyricum regulates the amount and functional status of LPDCs in the intestinal mucosa of mice with IBS, and therefore modulates the local immune response in the intestine.


Assuntos
Clostridium butyricum/imunologia , Células Dendríticas/imunologia , Mucosa Intestinal/imunologia , Síndrome do Intestino Irritável/terapia , Probióticos/administração & dosagem , Animais , Modelos Animais de Doenças , Humanos , Imunidade nas Mucosas , Mucosa Intestinal/citologia , Mucosa Intestinal/microbiologia , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento , Ácido Trinitrobenzenossulfônico/toxicidade
15.
J Strength Cond Res ; 33(11): 3129-3135, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31644518

RESUMO

Orysiak, J, Witek, K, Malczewska-Lenczowska, J, Zembron-Lacny, A, Pokrywka, A, and Sitkowski, D. Upper respiratory tract infection and mucosal immunity in young ice hockey players during the pretournament training period. J Strength Cond Res 33(11): 3129-3135, 2019-The aim of this study was to determine the effects of 17 days of training during preparation for the Ice Hockey Under 18 World Championship of the Polish ice hockey national team on the mucosal immune function and monitor upper respiratory tract infection (URTI) incidence before, during, and after the competition. Twelve male ice hockey players (age, 17.7 ± 0.5 years) were recruited for this study. The first saliva and blood collection took place at the beginning of the training camp (without training at the training camp), the second one was collected on the 9th day of the training camp immediately after the intensification of training, and the third collection was performed on the 13th day of training (4 days before leaving for the World Championship) in the tapering phase. To assess the mucosal immune function, concentrations of secretory immunoglobulin A (sIgA), sIgA1, and sIgA2 were analyzed in saliva. Cortisol concentration and creatine kinase activity were determined in blood, as indicators of stress and muscle damage, respectively. The Wisconsin Upper Respiratory Symptom Survey-21 questionnaire was used to assess URTI symptoms. A significant increase in the sIgA1 and sIgA2 concentrations was observed in the third collection compared with the second time point (114.45 ± 33.00 vs. 77.49 ± 27.29 and 88.97 ± 25.33 vs. 71.65 ± 32.44 U, respectively). There were no statistically significant correlations between the URTI incidence and saliva variables. In conclusion, the tapering period positively affects the mucosal immune function, especially sIgA1 and sIgA2 concentrations, with no significant change in the frequency of URTI in young ice hockey players.


Assuntos
Hóquei/fisiologia , Imunidade nas Mucosas , Imunoglobulina A Secretora/metabolismo , Condicionamento Físico Humano/fisiologia , Infecções Respiratórias/imunologia , Adolescente , Creatina Quinase/sangue , Humanos , Hidrocortisona/sangue , Incidência , Masculino , Saliva/metabolismo , Inquéritos e Questionários , Avaliação de Sintomas
16.
Immunity ; 51(5): 871-884.e6, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31628054

RESUMO

Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deficiency of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived interleukin-22 (IL-22) production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22+ CCR6+ ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings suggest that Ffar2 regulates colonic ILC3 proliferation and function, and they identify an ILC3-receptor signaling pathway modulating gut homeostasis and pathogen defense.


Assuntos
Imunidade Inata , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Biomarcadores , Citocinas/metabolismo , Suscetibilidade a Doenças , Microbioma Gastrointestinal/imunologia , Expressão Gênica , Humanos , Imunomodulação , Mucosa Intestinal/patologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas c-akt , Receptores de Superfície Celular/agonistas , Fator de Transcrição STAT3/metabolismo
17.
Int J Nanomedicine ; 14: 8179-8193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632026

RESUMO

Background: Chlamydia psittaci is a zoonotic bacteria closely associated with psittacosis/ornithosis. Vaccination has been recognized as the best way to inhibit the spread of C. psittaci due to the majority ignored of infections. The optimal Chlamydia vaccine was obstructed by the defect of single immunization route and the lack of availability of nontoxic and valid adjuvants. Methods: In this study, we developed a novel immunization strategy, simultaneous (SIM) intramuscular (IM) and intranasal (IN) administration of a C. psittaci antigens (Ags) adjuvanted with chitosan nanoparticles (CNPs). And SIM-CNPs-Ags were used to determine the different types of immune response and the protective role in vivo. Results: CNPs-Ags with zeta-potential values of 13.12 mV and of 276.1 nm showed excellent stability and optimal size for crossing the mucosal barrier with high 71.7% encapsulation efficiency. SIM-CPN-Ags mediated stronger humoral and mucosal responses by producing meaningfully high levels of IgG and secretory IgA (sIgA) antibodies. The SIM route also led to Ags-specific T-cell responses and increased IFN-γ, IL-2, TNF-α and IL-17A in the splenocyte supernatants. Following respiratory infection with C. psittaci, we found that SIM immunization remarkably reduced bacterial load and the degree of inflammation in the infected lungs and made for a lower level of IFN-γ, TNF-α and IL-6. Furthermore, SIM vaccination with CNPs-Ags had obviously inhibited C. psittaci disseminating to various organs in vivo. Conclusion: SIM immunization with CNPs-adjuvanted C. psittaci Ags may present a novel strategy for the development of a vaccine against the C. psittaci infection.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Quitosana/administração & dosagem , Chlamydophila psittaci/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Nanopartículas/administração & dosagem , Administração Intranasal , Animais , Antígenos de Bactérias/imunologia , Citocinas/metabolismo , Feminino , Imunidade Humoral , Imunidade nas Mucosas , Imunoglobulina G/metabolismo , Injeções Intramusculares , Pulmão/patologia , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Tamanho da Partícula , Psitacose , Baço/imunologia , Baço/microbiologia , Linfócitos T/imunologia , Vacinação
18.
Molecules ; 24(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600890

RESUMO

In this study, an acidic polysaccharide from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-ß-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of ß-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4+/CD8+ T lymphocyte ratio. These results suggest that ß-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.


Assuntos
Codonopsis/química , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Hidrólise , Imunidade nas Mucosas/efeitos dos fármacos , Fatores Imunológicos/química , Camundongos , Estrutura Molecular , Monossacarídeos/química , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Análise Espectral
19.
Jpn J Clin Oncol ; 49(9): 877-880, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613356

RESUMO

We developed an HPV16 E7-expressing Lactobacillus-based therapeutic vaccine, IGMKK16E7, to elicit mucosal E7-specific TH1 cellular immune responses. This study aims to examine the safety and clinical efficacy of IGMKK16E7 on HPV16-positive high-grade squamous intraepithelial lesion (HSIL). This is a multicenter, placebo-controlled, double-blind randomized phase I/II trial to test the safety and efficacy of IGMKK16E7 against HPV16-positive HSIL. The groups will include placebo, low-dose (0.5 g/day), middle-dose (1 g/day), and high-dose (1.5 g/day) IGMKK16E7. The target sample size will be 41 patients per group, and our data on our former agent, GLBL101c, were used to calculate sample size for 70% power and an α level = 0.05. The primary endpoint is IGMKK16E7 safety and pathological regression at week 16, and the secondary endpoints are cytological regression and HPV16 E7 immunological response. This study protocol has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. Patient enrollment will begin in May 2019.


Assuntos
Papillomavirus Humano 16 , Imunoterapia , Proteínas E7 de Papillomavirus/imunologia , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/uso terapêutico , Lesões Intraepiteliais Escamosas Cervicais/terapia , Adulto , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Método Duplo-Cego , Feminino , Humanos , Imunidade nas Mucosas , Lactobacillus/genética , Pessoa de Meia-Idade , Lesões Intraepiteliais Escamosas Cervicais/imunologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Resultado do Tratamento , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
20.
Mol Immunol ; 114: 497-512, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31518854

RESUMO

Compounding with the problem of frequent antigenic shift and occasional drift of the segmented genome of Avian Influenza Virus (AIV), vaccines based on major surface glycoproteins such as haemagglutinin (HA) to counter heterosubtypic AIV infection in chickens remain unsuccessful. In contrast, neuraminidase (NA), the second most abundant surface glycoprotein present in viral capsid is less mutable and, in some instances, successful in eliciting inter-species cross-reactive antibody responses. However, without selective activation of B-cells and T-cells, the ability of NA to induce strong cell mediated immune responses is limited, thus NA based vaccines cannot singularly address the risk of virus escape from host defence. To this end, the highly conserved ectodomain of influenza matrix protein-2 (M2e) has emerged as an attractive cross-protective vaccine target. The present study describes the potential of recombinant Lactococcus lactis (rL. lactis) in expressing functional influenza NA or M2e proteins and conferring effective mucosal and systemic immune responses in the intestine as well as in the upper respiratory airways (trachea) of chickens. In addition, lavages collected from trachea and intestine of birds administered with rL. lactis expressing influenza NA or M2e protein were found to protect MDCK cells against avian influenza type A/PR/8/34 (H1N1) virus challenge. Although minor, the differences in the expression of pro-inflammatory cytokines gene transcripts targeted in this study among the birds administered with either empty or rL. lactis could be attributed to the activation of innate response by L. lactis.


Assuntos
Galinhas/imunologia , Imunidade nas Mucosas/imunologia , Influenza Aviária/imunologia , Lactococcus lactis/imunologia , Neuraminidase/imunologia , Proteínas da Matriz Viral/imunologia , Animais , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Galinhas/virologia , Reações Cruzadas/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Linfócitos T/imunologia , Vacinação/métodos
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