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1.
Nat Commun ; 11(1): 4475, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901029

RESUMO

Tissue resident memory CD8+ T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunidade nas Mucosas , Administração Oral , Animais , Antígenos/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Quimiotaxia/imunologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Memória Imunológica , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/administração & dosagem , Estreptomicina/administração & dosagem
2.
Mol Immunol ; 126: 65-72, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32768860

RESUMO

The insect gut participates in initial local immune responses by producing reactive oxygen and nitrogen species as well as anti-microbial peptides to resist pathogenic invasions. Nitric oxide (NO), a signaling and an immune effector molecule synthesized by the enzyme NO synthase (NOS), mediates an early step of the signal transduction pathway. In this study, we evaluated NO levels after Nosema pernyi infection in Antheraea pernyi gut. NOS activity was higher in the microsporidia-infected gut of A. pernyi than in that of control. Three NOS-related genes were cloned, and their spatio-temporal expression patterns were evaluated. ApNOS2 was expressed quickly in the midgut after N. pernyi infection. Sodium nitroprusside, dihydrate (SNP), or Nω-L-nitro-arginine methyl ester, hydrochloride (L-NAME), altered the NO content in A. pernyi midgut. Anti-microbial peptides (AMPs) in the groups exposed to N. pernyi plus SNP and N. pernyi plus L-NAME exhibited higher and lower expression, respectively, relative to the control. These results indicate that microsporidia infection triggers short-term activation of NO and NOS genes in the A. pernyi gut that is downregulated after 24 h. Notably, infection rates can be influenced by a NOS inhibitor. Furthermore, NO can be induced by pathogens. Similarly, NO content in the A. pernyi gut also influences AMPs in humoral immunity and some immune-related genes. Our results suggest that nitric oxide plays a vital role in A. pernyi gut immunity.


Assuntos
Trato Gastrointestinal/imunologia , Microsporidiose/veterinária , Mariposas/imunologia , Óxido Nítrico/metabolismo , Nosema/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Artrópodes/antagonistas & inibidores , Proteínas de Artrópodes/metabolismo , Regulação para Baixo , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Imunidade Humoral/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Microsporidiose/imunologia , Mariposas/enzimologia , Mariposas/microbiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Análise Espaço-Temporal
3.
Toxicol Lett ; 333: 115-129, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758513

RESUMO

Despite many studies investigating the mechanism of Sulfur Mustard (SM) induced lung injury, the underlying mechanism is still unclear. Inflammatory and subsequent fibroproliferative stages of SM-toxicity are based upon several highly-related series of events controlled by the immune system. The inhalation of SM gas variably affects different cell populations within the lungs. Various studies have shown the critical role of macrophages in triggering a pulmonary inflammatory response as well as its maintenance, resolution, and repair. Importantly, macrophages can serve as either pro-inflammatory or anti-inflammatory populations depending on the present conditions at any pathological stage. Different characteristics of macrophages, including their differentiation, phenotypic, and functional properties, as well as interactions with other cell populations determine the outcomes of lung diseases and the extent of long- or short-term pulmonary damage induced by SM. In this paper, we summarize the current state of knowledge regarding the role of alveolar macrophages and their mediators in the pathogenesis of SM in pulmonary injury. Investigating the specific cells and mechanisms involved in SM-lung injury may be useful in finding new target opportunities for treatment of this injury.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Substâncias para a Guerra Química/toxicidade , Imunidade Inata/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Gás de Mostarda/toxicidade , Animais , Humanos , Pulmão/imunologia , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia
4.
Toxicol Lett ; 333: 159-169, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32783910

RESUMO

The intestinal epithelium is the first barrier against food contaminants and is highly sensitive to Fusarium toxins, especially deoxynivalenol (DON) and zearalenone (ZEA). Here, we explored the effects of low doses of DON and/or ZEA in naturally moldy diets on intestinal functions in piglets, including inflammatory responses, epithelial barrier, and microbial composition. Piglets were treated with a control diet (CON), DON diet (1000.6 µg/kg), ZEA diet (269.1 µg/kg), and DON + ZEA diet (1007.5 + 265.4 µg/kg), respectively, for 3 weeks and then switched to the same CON diet for another 2 weeks. In the first period, even the selected low doses of DON or ZEA in the diet resulted in intestinal inflammation, diminish protein expression (claudin-4) and altered gut microbiota populations. Whereas upon switching to the CON diet for another 2 weeks, the deleterious effect of ZEA and DON on IL-1ß and Bifidobacterium population could not be recovered. Additionally, combined DON and ZEA negatively affected body weight gain and feed consumption of piglets, as well as shown synergistic effects on evoking pro-inflammatory cytokines contents (TNF-α, IL-1ß, and IL-6) and perturbing the cecum microbiota profile (E. coli, Lactobacillus, and Bifidobacterium). Collectively, chronic consumption of DON and ZEA contaminated feed or food, even at low doses, can induce intestinal damage and may have consequences for animal and human health.


Assuntos
Ração Animal/microbiologia , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Suínos , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/imunologia , Ceco/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Dieta , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Contaminação de Alimentos/análise , Fusarium/crescimento & desenvolvimento , Fusarium/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Hordeum/microbiologia , Inflamação , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Jejuno/efeitos dos fármacos , Jejuno/imunologia , Jejuno/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Zea mays/microbiologia
5.
Am J Trop Med Hyg ; 103(3): 1032-1038, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32720632

RESUMO

Transcutaneous vaccination can induce both mucosal and systemic immune responses. However, there are few data on anti-polysaccharide responses following transcutaneous vaccination of polysaccharides, despite the role that anti-polysaccharide responses play in protecting against intestinal mucosal and respiratory pathogens. Whether transcutaneous vaccination with a conjugate polysaccharide vaccine would be able to induce memory responses is also unknown. To address this, we transcutaneously vaccinated mice with virulence antigen (Vi) polysaccharide of Salmonella enterica serovar Typhi (the cause of typhoid fever), either in unconjugated or conjugated form (the latter as a Vi-DT conjugate). We also assessed the ability of the immunoadjuvant cholera toxin to impact responses following vaccination. We found that presenting Vi in a conjugate versus nonconjugate form transcutaneously resulted in comparable serum IgG responses but higher serum and lamina propria lymphocyte IgA anti-Vi responses, as well as increased IgG memory responses. The addition of immunoadjuvant did not further increase these responses; however, it boosted fecal IgA and serum IgG anti-Vi responses. Our results suggest that transcutaneous vaccination of a conjugate vaccine can induce systemic as well as enhanced mucosal and memory B-cell anti-polysaccharide responses.


Assuntos
Anticorpos Antibacterianos/sangue , Imunidade Humoral/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Salmonella typhi/imunologia , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/administração & dosagem , Vacinação/métodos , Administração Cutânea , Animais , Modelos Animais de Doenças , Feminino , Humanos , Esquemas de Imunização , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Memória Imunológica/efeitos dos fármacos , Camundongos , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/imunologia , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/patogenicidade , Febre Tifoide/imunologia , Febre Tifoide/microbiologia , Vacinas Tíficas-Paratíficas/biossíntese , Vacinas Conjugadas
6.
Carbohydr Polym ; 235: 115957, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122493

RESUMO

The present study aimed to investigate the protective effect of cultured Cordyceps sinensis polysaccharides (CSP) on cyclophosphamide (Cy)-induced intestinal mucosal immunosuppression and microbial dysbiosis in mice. Results showed that CSP stimulated cytokines secretion (IL-12, IFN-γ, IL-4, IL-13, IL-6, IL-17, IL-10, TGF-ß3, TNF-α, IL-2, IL-21) and transcription factors production (T-bet, GATA-3, RORγt, Foxp3). TLRs (TLR-2, TLR-4, TLR-6) and NF-κB pathway key proteins (p-IκB-α, NF-κB p65) were also upregulated after CSP administration. Moreover, CSP recovered SCFAs levels which decreased by Cy treatment. Furthermore, 16S rRNA sequencing of fecal samples was performed. α-diversity and ß-diversity analysis revealed CSP improved microbial community diversity and modulated the overall structure of gut microbiota. Taxonomic composition analysis found that CSP increased the abundance of probiotics (Lactobacillus, Bifidobacterium, Bacteroides) and decreased pathogenic bacteria (Clostridium, Flexispira). These findings suggested the potential of CSP as a prebiotics to reduce side effects of Cy on intestinal mucosal immunity and gut microbiota.


Assuntos
Cordyceps/química , Ciclofosfamida/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Feminino , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Polissacarídeos/química , Substâncias Protetoras/química , Propriedades de Superfície
7.
PLoS One ; 15(2): e0228463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027689

RESUMO

Infection with Brucella abortus causes contagious zoonosis, brucellosis, and leads to abortion in animals and chronic illness in humans. Chitosan nanoparticles (CNs), biocompatible and nontoxic polymers, acts as a mucosal adjuvant. In our previous study, B. abortus malate dehydrogenase (Mdh) was loaded in CNs, and it induced high production of pro-inflammatory cytokines in THP-1 cells and systemic IgA in BALB/C mice. In this study, the time-series gene expression analysis of nasal-associated lymphoid tissue (NALT) was performed to identify the mechanism by which Mdh affect the target site of nasal immunization. We showed that intranasal immunization of CNs-Mdh reduced cell viability of epithelial cells and muscle cells at first 1 h, then induced cellular movement of immune cells such as granulocytes, neutrophils and lymphocytes at 6h, and activated IL-6 signaling pathway at 12h within NALT. These activation of immune cells also promoted signaling pathway for high-mobility group box 1 protein (HMGB1), followed by the maturation of DCs required for mucosal immunity. The CNs also triggered the response to other organism and inflammatory response, showing it is immune-enhancing adjuvant. The ELISA showed that significant production of specific IgA was detected in the fecal excretions and genital secretions from the CNs-Mdh-immunized group after 2 weeks-post immunization. Collectively, these results suggest that B. abortus Mdh-loaded CNs triggers activation of HMGB1, IL-6 and DCs maturation signaling within NALT and induce production of systemic IgG and IgA.


Assuntos
Formação de Anticorpos/fisiologia , Brucella abortus/imunologia , Brucelose/prevenção & controle , Imunização/métodos , Tecido Linfoide/imunologia , Malato Desidrogenase/imunologia , Administração Intranasal , Animais , Formação de Anticorpos/efeitos dos fármacos , Brucella abortus/metabolismo , Brucelose/imunologia , Quitosana/administração & dosagem , Quitosana/química , Quitosana/imunologia , Quitosana/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunogenicidade da Vacina , Tecido Linfoide/efeitos dos fármacos , Malato Desidrogenase/administração & dosagem , Malato Desidrogenase/metabolismo , Malato Desidrogenase/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia
8.
Am J Physiol Gastrointest Liver Physiol ; 318(3): G542-G553, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31984787

RESUMO

A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal , Imunidade Inata , Imunidade nas Mucosas , Mucosa Intestinal/metabolismo , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Vitamina D/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/imunologia , Síndrome Metabólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Receptores de Calcitriol/metabolismo , Transdução de Sinais , Vitamina D/uso terapêutico
9.
Fish Shellfish Immunol ; 96: 254-261, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31839587

RESUMO

The dietary effects of a native medicinal plant from Iran, common mallow (Malvae sylvestris), was evaluated on growth performance, innate immune parameters, mucosal immune parameters, and resistance of rainbow trout (Oncorhynchus mykiss) against Yersinia ruckeri. Therefore, 360 fish (initial weight 10.42 ± 0.09 g) were randomly distributed into 12 fiberglass tanks. Experimental diets supplemented with 0 (as control- C), 1% (M1), 3% (M2) and 5% (M3) levels of M. sylvestris flowers extract were fed to the fish based on 3% of body weight for 8 weeks. At the terminal sampling, growth performance, liver and digestive enzymes activities, blood and mucosal immune responses were determined. Results showed that M2 and M3 had greater final weight, weight gain, SGR, survival rate and lower FCR; higher levels of total protein, albumin, globulin, and lower cortisol levels in comparison to control; 5% extract also lowered cholesterol and glucose levels as well as Lactate Dehydrogenase (LDH) activity. We reported higher values of hematocrit, hemoglobin, Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Volume (MCV), White Blood Cell (WBC), Red Blood Cell (RBC) and lymphocytes for treated groups. Innate immune responses (Alternative complement activity (ACH50) in M2 and M3 group, total Immunoglobulin (Ig) and lysozyme in M3), mucosal immune parameters (ACH50, total Ig for M2 and M3 group and lysozyme in all treated groups) were enhanced. Activities of digestive enzymes (protease in all treated groups, amylase for 3 and 5%, while lipase only for 5%) and lower activity of liver ALT enzyme in individuals treated with highest dose was observed. Overall results indicated that the extract can positively affect growth performance and immune responses of rainbow trout.


Assuntos
Resistência à Doença , Doenças dos Peixes/imunologia , Imunidade Inata , Malva/química , Oncorhynchus mykiss/imunologia , Extratos Vegetais/farmacologia , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Resistência à Doença/efeitos dos fármacos , Relação Dose-Resposta a Droga , Imunidade Inata/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Oncorhynchus mykiss/crescimento & desenvolvimento , Distribuição Aleatória , Yersiniose/imunologia , Yersiniose/veterinária , Yersinia ruckeri/fisiologia
10.
Immunol Res ; 67(4-5): 398-407, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31773490

RESUMO

Limited protective effects of commercially available vaccines necessitate the development of novel pneumococcal vaccines. We recently reported a pneumococcal systemic vaccine containing two proteins, Pneumococcal surface protein A (PspA of family 1 and 2) and a bacterium-like particle-based pneumococcal mucosal vaccine containing PspA2 and PspA4 fragments, both eliciting broad protective immune responses. We had previously reported that subcutaneous (s.c.+s.c.+s.c.) immunization with the systemic vaccine induced more pronounced humoral serum IgG responses, while intranasal (i.n.+i.n.+i.n.) immunization with the mucosal vaccine elicited a more pronounced mucosal secretory IgA (sIgA) response. We hypothesized that a combinatorial administration of the two vaccines might elicit more pronounced and broader protective immune responses. Therefore, this study aimed to determine the efficacy of combinatorial prime-boost immunization using both systemic and mucosal vaccines for a pneumococcal infection. Combinatorial prime-boost immunization (s.c.+i.n. and i.n.+s.c.) induced not only IgG, but also mucosal sIgA production at high levels. Systemic priming and mucosal boosting immunization (s.c.+i.n.) provided markedly better protection than homologous prime-boost immunization (s.c.+s.c.+s.c. and i.n.+i.n.+i.n.). Moreover, it induced more robust Th1 and Th17 cell-mediated immune responses than mucosal priming and systemic boosting immunization (i.n.+s.c.). These results indicate that combinatorial prime-boost immunization potentially induces a robust systemic and mucosal immune response, making it an optimal alternative for maximum protection against lethal pneumococcal infections.


Assuntos
Proteínas de Bactérias/farmacologia , Imunidade Celular/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Imunização Secundária , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/farmacologia , Streptococcus pneumoniae/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/imunologia , Feminino , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/patologia , Vacinas Pneumocócicas/imunologia , Células Th1/imunologia , Células Th17/imunologia
11.
Nutrients ; 11(10)2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31590415

RESUMO

In preterm newborns the immaturity of the immune system is remarkable, with reduced innate and adaptive immune responses. Many bioactive compounds in breast milk, such as growth factors and adipokines, contribute to the immune system's maturation in early life. However, studies on the immunoregulatory activity in preterm neonates are practically nonexistent. The aim of the present study was to determine whether a nutritional supplementation in early life with leptin or epidermal growth factor (EGF) was able to promote the maturation of the systemic and intestinal immune system in preterm conditions. For this purpose, premature rats were daily supplemented by oral gavage with leptin or EGF. Term and Preterm groups receiving vehicle were used as controls. Preterm rats showed deficiencies compared to full-term ones, such as lower body weights, erythrocyte counts, plasma IgG and IgM concentrations and B cell percentages, and higher values of Th and Tc TCRαß+ cells in mesenteric lymph nodes, and intestinal permeability, among others. However, leptin and EGF supplementation were able to revert some of these deficiencies and to improve the premature immune system's development. These results suggest that leptin and EGF are involved in enhancing the maturation of the systemic and intestinal immune system in preterm conditions.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Suplementos Nutricionais , Fator de Crescimento Epidérmico/farmacologia , Imunidade Inata/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Lactação , Leptina/farmacologia , Linfonodos/efeitos dos fármacos , Nascimento Prematuro , Fatores Etários , Animais , Animais Lactentes , Feminino , Idade Gestacional , Imunidade nas Mucosas/efeitos dos fármacos , Imunoglobulinas/sangue , Intestino Delgado/crescimento & desenvolvimento , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Linfonodos/crescimento & desenvolvimento , Linfonodos/imunologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Permeabilidade , Fagócitos/imunologia , Fagocitose/efeitos dos fármacos , Gravidez , Ratos Wistar , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo
12.
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
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.
Nutrients ; 11(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581570

RESUMO

In physiological conditions, the gut is heavily infiltrated with various subsets of inflammatory cells, whose activity is tightly controlled by counter-regulatory mechanisms. Defects in such mechanisms can favour the development of chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis (UC), the principal forms of inflammatory bowel diseases (IBD) in humans, as well as systemic disorders. Over the last years, the frequency of intestinal and systemic immune-inflammatory disorders has increased in previously low incidence areas, likely due to the Westernization of lifestyles, including dietary habits. The Western diet is characterized by high consumption of proteins, saturated fats and sweets, as well as by a broad use of food additives (e.g., emulsifiers, bulking agents), which are used to preserve and enhance food quality. Accumulating evidence suggests that food additives can perturb gut homeostasis, thereby contributing to promote tissue-damaging inflammatory responses. For instance, mice given the emulsifiers carboxymethylcellulose and polysorbate 80 develop dysbiosis with overgrowth of mucus-degrading bacteria. Such an effect triggers colitis in animals deficient in either interleukin-10, a cytokine exerting anti-inflammatory and regulatory functions, or Toll-like receptor 5, a receptor recognizing the bacterial flagellin. Similarly, the polysaccharide maltodextrin induces endoplasmic reticulum stress in intestinal goblet cells, thereby impairing mucus release and increasing host susceptibility to colitis. In this review, we report and discuss the current knowledge about the impact of food additives on gut homeostasis and their potential contribution to the development of inflammatory disorders.


Assuntos
Colite/induzido quimicamente , Dieta Ocidental/efeitos adversos , Aditivos Alimentares/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Doenças Metabólicas/induzido quimicamente , Animais , Colite/epidemiologia , Colite/imunologia , Colite/microbiologia , Disbiose , Homeostase , Humanos , Intestinos/imunologia , Intestinos/microbiologia , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/imunologia , Doenças Metabólicas/microbiologia , Medição de Risco , Fatores de Risco
15.
PLoS One ; 14(9): e0222878, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31550271

RESUMO

INTRODUCTION: Mucosal immune activation, in the context of sexual transmission of HIV-1 infection, is crucial, as the increased presence of activated T cells enhance susceptibility to infection. In this regard, it has been proposed that immunomodulatory compounds capable of modulating immune activation, such as Vitamin D (VitD) may reduce HIV-1 transmission and might be used as a safe and cost-effective strategy for prevention. Considering this, we examined the in vitro effect of the treatment of peripheral blood mononuclear cells (PBMCs) with the active form of VitD, calcitriol, on cellular activation, function and susceptibility of CD4+ T cells to HIV-1 infection. METHODS: We treated PBMCs from healthy HIV unexposed individuals (Co-HC) and frequently exposed, HIV-1 seronegative individuals (HESNs) from Colombia and from healthy non-exposed individuals from Canada (Ca-HC) with calcitriol and performed in vitro HIV-1 infection assays using X4- and R5-tropic HIV-1 strains respectively. In addition, we evaluated the activation and function of T cells and the expression of viral co-receptors, and select antiviral genes following calcitriol treatment. RESULTS: Calcitriol reduced the frequency of infected CD4+ T cells and the number of viral particles per cell, for both, X4- and R5-tropic viruses tested in the Co-HC and the Ca-HC, respectively, but not in HESNs. Furthermore, in the Co-HC, calcitriol reduced the frequency of polyclonally activated T cells expressing the activation markers HLA-DR and CD38, and those HLA-DR+CD38-, whereas increased the subpopulation HLA-DR-CD38+. Calcitriol treatment also decreased production of granzyme, IL-2 and MIP-1ß by T cells and increased the transcriptional expression of the inhibitor of NF-kB and the antiviral genes cathelicidin (CAMP) and APOBEC3G in PBMCs from Co-HC. CONCLUSION: Our in vitro findings suggest that VitD treatment could reduce HIV-1 transmission through a specific modulation of the activation levels and function of T cells, and the production of antiviral factors. In conclusion, VitD remains as an interesting potential strategy to prevent HIV-1 transmission that should be further explored.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Calcitriol/administração & dosagem , Infecções por HIV/prevenção & controle , Ativação Linfocitária/efeitos dos fármacos , Vitaminas/administração & dosagem , Desaminase APOBEC-3G/imunologia , Desaminase APOBEC-3G/metabolismo , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Feminino , Infecções por HIV/sangue , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/patogenicidade , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Humanos , Imunidade nas Mucosas/efeitos dos fármacos , Masculino , Cultura Primária de Células
16.
Fish Shellfish Immunol ; 94: 407-416, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521784

RESUMO

The aims of this study were to investigate the antibacterial, immunostimulatory and antioxidant properties of different derivatives of Oliveria decumbens, in vitro and in vivo. The GC-MS spectrometry analysis showed γ-terpinene as the most frequent compound in essential oil, whereas carvacrol and thymol were the most common ones in aromatic water. Plant essential oil and hydroethanolic extract showed a positive in vitro bactericidal activity against Streptococcus iniae as evaluated by disc diffusion, minimum inhibitory concentration and minimum bactericidal concentration methods. Also, in vivo resistance against S. iniae and immune and antioxidant responses of Nile tilapia (Oreochromis niloticus) were assayed after 60 days treatment with O. decumbens derivatives. Plant hydroethanolic extract and essential oil and their 1:1 combination were added to diet at 0 (negative control), 0.01, 0.1 and 1% (w:w). The plant aromatic water at doses of 0.0312, 0.0625 and 0.1250% were also used as bath treatment. The results showed that aromatic water at lowest dose was more effective than other treatments in increment of fish resistance against S. iniae (7.14% mortality in comparison with 50% mortalities in control fish) and modulation of post-challenge respiratory burst activity. The bactericidal activity and biochemical contents of skin mucus did not change significantly among treatments. The levels of superoxide dismutase and catalase antioxidant enzymes activities in spleen tissue were significantly higher in treatments received extract, essential oils and their combination in comparison to other groups, while treatments did not affect peroxidase level. In conclusion, administration of different derivatives of Oliveria decumbens showed remarkable antibacterial activity against streptococcosis and enhanced antioxidant status and post-challenge immunity in Nile tilapia.


Assuntos
Adjuvantes Imunológicos/farmacologia , Antibacterianos/farmacologia , Apiaceae/química , Ciclídeos/imunologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Streptococcus iniae/efeitos dos fármacos , Adjuvantes Imunológicos/química , Ração Animal/análise , Animais , Antibacterianos/química , Antioxidantes/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Resistência à Doença/imunologia , Relação Dose-Resposta a Droga , Doenças dos Peixes/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Óleos Voláteis/química , Extratos Vegetais/química , Soro/efeitos dos fármacos , Soro/imunologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Streptococcus iniae/fisiologia
17.
Fish Shellfish Immunol ; 94: 705-710, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505247

RESUMO

The present study investigates the effect of dietary Ziziphus jujube fruit extract [ZJFE] on skin mucus non-specific immune parameters as well as mRNA levels of immune related gene in the skin of common carp fingerlings. An eight-week feeding trial was performed using different levels of dietary ZJFE (0, 0.25, 0.5 and 1%). At the end of the trial skin mucus immune parameters (total Ig, lysozyme and protease activity), cytokines genes (il1b, il8, il10 and tnf-alpha) expression in skin and growth performance were studied. The result showed highest and lowest skin mucus total Ig were observed in fish fed diet containing 0.5% ZJFE and control group, respectively (P < 0.05). There were no significant difference among treatments regarding skin mucus lysozyme activity (P >0.05). It should be noted that, feeding on 0.5 and 1% ZJFE significantly increased skin mucus protease activity (P <0.05). Likewise, gene expression studies in skin showed significant increase of il1b expression in fish fed 0.5% ZJFE compared other treatments (P <0.05). Also, il8 gene was noticeably up-regulated in 0.5 and 1% treatments compared to the control group (P <0.05). While there were no significant difference between 0.25% JFE treatment and control in case of relative il10 gene expression (P >0.05), feeding on diets containing 0.5% or 1% ZJFE significantly down-regulated il10 gene (P <0.05). Our study indicated that relative expression of tnf-alpha gene significantly increased in treated groups (P <0.05). Also, feeding on ZJFE supplemented diet improved growth performance parameters. Overall, this experiment demonstrated the potentially useful effects of ZJFE on skin mucosal immunity and performance of common carp fingerlings.


Assuntos
Carpas/imunologia , Expressão Gênica/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Extratos Vegetais/metabolismo , Ração Animal/análise , Animais , Carpas/genética , Carpas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Frutas/química , Extratos Vegetais/administração & dosagem , Pele/imunologia , Pele/metabolismo , Ziziphus/química
18.
PLoS One ; 14(8): e0221181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31437197

RESUMO

Globally, HIV/AIDS is a leading cause of morbidity worldwide among reproductive-aged cisgender women, highlighting the importance of understanding effects of contraceptives on HIV-1 risk. Some observational studies suggest there may be an increased risk of HIV-1 acquisition among women using the long-acting injectable progestin contraceptive, depo-medroxyprogesterone acetate. The potential mechanism of this susceptibility is unclear. There are few data on the role of the upper female reproductive tract in HIV-1 transmission, and the mechanisms of HIV-1 infection are likely to differ in the upper compared to the lower reproductive tract due to differences in tissue composition and variable effects of sex steroids on mucosal immune cell distribution and activity. In this study, we measured the susceptibility of mucosal immune cells from the upper female reproductive tract to HIV-1 entry using the virion-based HIV-1 fusion assay in samples from healthy female volunteers. We studied 37 infectious molecular clones for their ability to fuse to cells from endometrial biopsies in three participants and found that subtype (B or C) and origin of the virus (transmitted founder or chronic control) had little influence on HIV-1 fusion susceptibility. We studied the effect of contraceptives on HIV-1 susceptibility of immune cells from the cervix, endometrium and peripheral blood by comparing fusion susceptibility in four groups: users of the copper intrauterine device (IUD), levonorgestrel-containing oral contraceptive, levonorgestrel-containing IUD and unexposed controls (n = 58 participants). None of the contraceptives was associated with higher rates of HIV-1 entry into female reproductive tract cells compared to control samples from the mid-luteal phase.


Assuntos
Antivirais/farmacologia , Contraceptivos Hormonais/farmacologia , Células Epiteliais/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Dispositivos Intrauterinos , Levanogestrel/farmacologia , Adolescente , Adulto , Biópsia , Anticoncepção/métodos , Estudos Transversais , Endométrio/citologia , Endométrio/imunologia , Células Epiteliais/imunologia , Células Epiteliais/virologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Fibroblastos/virologia , HIV-1/fisiologia , Humanos , Imunidade nas Mucosas/efeitos dos fármacos , Dispositivos Intrauterinos de Cobre , Fase Luteal/fisiologia , Pessoa de Meia-Idade , Cultura Primária de Células , Internalização do Vírus/efeitos dos fármacos
19.
Poult Sci ; 98(12): 6400-6410, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424515

RESUMO

This study was aimed to assess the protective effects of γ-irradiated Astragalus polysaccharides (IAPS) on the development of small intestine and intestinal mucosal immunity of immunosuppressed broilers induced by cyclophosphamide (CPM). A total of 384 one-day-old broiler chicks with similar initial weight were randomly assigned into 6 groups: non-treated group (control), and CPM-treated groups fed either a basal diet or the diets containing 900 mg/kg APS, or 900, 600, 300 mg/kg IAPS, respectively. On days 16, 18, and 20, all broilers except for control group were intramuscularly injected with 0.5 mL CPM (40 mg/kg of BW). Broilers in the control group were intramuscularly injected with 0.5 mL sterilized saline (0.75%, wt/vol). This trial was lasted for 21 d. The results revealed that both APS and IAPS treatment elevated the duodenal IgA-producing cells number and the jejunal mRNA expression of interleukin-2 (IL-2), interleukin-10 (IL-10), and interferon γ of CPM-injected broilers (P < 0.05). The decreased jejunal villus height (VH), the ratio of VH to crypt depth (V/C), as well as the intestinal intraepithelial lymphocytes (IELs) and goblet cells number in CPM-injected broilers were elevated by dietary supplementation with 900 mg/kg APS or 900, 600 mg/kg IAPS (P < 0.05). The CPM-induced decrease in jejunum index, the duodenal VH and the jejunal IgA-producing cells number were only improved in the 900 mg/kg IAPS group (P < 0.05). Furthermore, the number of IELs and IgA-producing cells in duodenum, VH, V/C, the number of goblet cells, and mRNA expression of IL-2 and IL-10 in jejunum were higher in the 900 mg/kg IAPS group than those in the 900 mg/kg APS group (P < 0.05). In summary, IAPS possessed stronger immunomodulatory effect than APS at the same supplementation level. Therefore, gamma irradiation can be used as an alternative treatment to enhance the immunomodulatory activity of APS.


Assuntos
Astrágalo (Planta)/química , Galinhas/fisiologia , Raios gama/efeitos adversos , Imunidade nas Mucosas , Intestinos/crescimento & desenvolvimento , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Ração Animal/análise , Animais , Galinhas/crescimento & desenvolvimento , Ciclofosfamida/efeitos adversos , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Imunidade nas Mucosas/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Imunossupressores/efeitos adversos , Intestinos/efeitos dos fármacos , Polissacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória
20.
Nutrients ; 11(9)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466230

RESUMO

Taste receptors, first identified on the tongue, are best known for their role in guiding our dietary preferences. The expression of taste receptors for umami, sweet, and bitter have been demonstrated in tissues outside of the oral cavity, including in the airway, brain, gastrointestinal tract, and reproductive organs. The extra-oral taste receptor chemosensory pathways and the endogenous taste receptor ligands are generally unknown, but there is increasing data suggesting that taste receptors are involved in regulating some aspects of innate immunity, and may potentially control the composition of the nasal microbiome in healthy individuals or patients with upper respiratory diseases like chronic rhinosinusitis (CRS). For this reason, taste receptors may serve as potential therapeutic targets, providing alternatives to conventional antibiotics. This review focuses on the physiology of sweet (T1R) and bitter (T2R) taste receptors in the airway and their activation by secreted bacterial products. There is particular focus on T2R38 in sinonasal ciliated cells, as well as the sweet and bitter receptors found on specialized sinonasal solitary chemosensory cells. Additionally, this review explores the impact of genetic variations in these receptors on the differential susceptibility of patients to upper airway infections, such as CRS.


Assuntos
Imunidade Inata , Imunidade nas Mucosas , Receptores Acoplados a Proteínas-G/metabolismo , Mucosa Respiratória/metabolismo , Sistema Respiratório/metabolismo , Infecções Respiratórias/metabolismo , Paladar , Animais , Antibacterianos/uso terapêutico , Bactérias/imunologia , Bactérias/metabolismo , Cílios/imunologia , Cílios/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/imunologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/microbiologia , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/imunologia , Sistema Respiratório/microbiologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Infecções Respiratórias/microbiologia , Transdução de Sinais , Paladar/efeitos dos fármacos
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