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1.
Food Res Int ; 136: 109577, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32846611

RESUMO

The year 2020 will be remembered by a never before seen, at least by our generation, global pandemic of COVID-19. While a desperate search for effective vaccines or drug therapies is on the run, nutritional strategies to promote immunity against SARS-CoV-2, are being discussed. Certain fermented foods and probiotics may deliver viable microbes with the potential to promote gut immunity. Prebiotics, on their side, may enhance gut immunity by selectively stimulating certain resident microbes in the gut. Different levels of evidence support the use of fermented foods, probiotics and prebiotics to promote gut and lungs immunity. Without being a promise of efficacy against COVID-19, incorporating them into the diet may help to low down gut inflammation and to enhance mucosal immunity, to possibly better face the infection by contributing to diminishing the severity or the duration of infection episodes.


Assuntos
Infecções por Coronavirus/terapia , Alimentos e Bebidas Fermentados , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Inflamação , Pneumonia Viral/terapia , Prebióticos , Probióticos , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Dieta , Trato Gastrointestinal/imunologia , Humanos , Inflamação/etiologia , Inflamação/microbiologia , Inflamação/prevenção & controle , Inflamação/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/microbiologia , Pneumonia Viral/virologia
2.
Virus Res ; 286: 198103, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32717345

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a major pandemic called coronavirus disease 2019 (COVID-19) that has created unprecedented global health emergencies, and emerged as a serious threat due to its strong ability for human-to-human transmission. The reports indicate the ability of SARS-CoV-2 to affect almost any organ due to the presence of a receptor known as angiotensin converting enzyme 2 (ACE2) across the body. ACE2 receptor is majorly expressed in the brush border of gut enterocytes along with the ciliated cells and alveolar epithelial type II cells in the lungs. The amino acid transport function of ACE2 has been linked to gut microbial ecology in gastrointestinal (GI) tract, thereby suggesting that COVID-19 may, to some level, be linked to the enteric microbiota. The significant number of COVID-19 patients shows extra-pulmonary symptoms in the GI tract. Many subsequent studies revealed viral RNA of SARS-CoV-2 in fecal samples of COVID-19 patients. This presents a new challenge in the diagnosis and control of COVID-19 infection with a caution for proper sanitation and hygiene. Here, we aim to discuss the immunological co-ordination between gut and lungs that facilitates SARS-CoV-2 to infect and multiply in the inflammatory bowel disease (IBD) and non-IBD patients.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Disbiose/imunologia , Trato Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/imunologia , Pulmão/imunologia , Pneumonia Viral/imunologia , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/microbiologia , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Disbiose/virologia , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/virologia , Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/virologia , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/microbiologia , Pneumonia Viral/virologia , Receptores Virais/genética , Receptores Virais/imunologia
3.
Virus Res ; 285: 198018, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32430279

RESUMO

Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. Role of the gut microbiota in influencing lung diseases has been well articulated. It is also known that respiratory virus infection causes perturbations in the gut microbiota. Diet, environmental factors and genetics play an important role in shaping gut microbiota which can influence immunity. Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/microbiologia , Microbioma Gastrointestinal , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Pneumonia Viral/imunologia , Pneumonia Viral/microbiologia , Envelhecimento , Infecções por Coronavirus/virologia , Dieta , Disbiose , Homeostase , Humanos , Imunidade , Pulmão/microbiologia , Pulmão/virologia , Pandemias , Pneumonia Viral/virologia
4.
J Anim Sci ; 98(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32300795

RESUMO

The objective of this experiment was to investigate the impact of an F18 enterotoxigenic Escherichia coli (ETEC) challenge on growth performance, aspects of intestinal function, and selected immune responses of piglets, as well as to evaluate potential protective effects of direct-fed microbial (DFM) blends. Seventy-two weaned piglets (6.4 ± 0.2 kg body weight [BW]; ~21 d of age) were assigned to one of four treatments: 1) NC: Nonchallenged (n = 10), 2) positive challenged control (PC): F18 ETEC-challenged (n = 10), 3) PC + DFM1 (n = 8; three strains of Bacillus amyloliquefaciens; 7.5 × 105 colony-forming units [cfu]/g), or 4) PC + DFM2 (n=8; 2 strains of B. amyloliquefaciens and one strain of Bacillus subtilis; 1.5 × 105 cfu/g). Feed intake and BW were recorded on day 0, 7, and 17. Pigs were sham-infected either with 6 mL phosphate-buffered saline or inoculated with 6 mL F18 ETEC (~1.9 × 109 cfu/mL) on day 7 (0 d postinoculation [dpi]). All ETEC-challenged pigs were confirmed to be genetically susceptible to F18. Pigs had ad libitum access to feed and water throughout the 17-d trial. Fecal scores were visually ranked and rectal temperatures were recorded daily. To evaluate ETEC shedding, fecal swabs were collected on dpi 0, 1, 2, 3, 5, 7, and 10. Blood samples were collected on dpi 0, 1, 2, 4, 7, and 10. Ileal tissues were collected at necropsy on dpi 10. All challenged treatments had lower final BW, decreased average daily gain (ADG), and average daily feed intake (ADFI) during the 10-d postchallenge period (P < 0.01). The DFM2 treatment increased E. coli shedding on dpi 2 and decreased iton dpi 7 (P < 0.05) compared with the PC. Rectal temperature decreased across all challenged treatments (P < 0.01). Ileal mRNA abundance of occludin (OCLN) and zonula occludens-1 (ZO-1) decreased in PC and DFM1 compared with NC (P < 0.05). Pigs fed DFM2 had intermediate ileal mRNA abundance of OCLN and increased ZO-1 mRNA compared with pigs in PC (P < 0.05). Interleukin 8 (IL-8) increased in the plasma of PC and DFM2 on dpi 2 compared with NC (P < 0.05). Mucosal IL-8 increased in PC compared with NC (P < 0.05). All challenged treatments tended to have elevated tumor necrosis factor-α (TNF-α) mRNA abundance compared with NC (P < 0.10). Challenged pigs had reduced secretory immunoglobulin A and villus height compared with NC pigs (P < 0.05). The impact of an ETEC challenge on intestinal function and the immune system has been revealed, information critical to developing improved treatment regimes.


Assuntos
Bacillus amyloliquefaciens/fisiologia , Bacillus subtilis/fisiologia , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/veterinária , Imunidade Inata , Probióticos/análise , Doenças dos Suínos/prevenção & controle , Animais , Derrame de Bactérias , Dieta/veterinária , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/prevenção & controle , Fezes/microbiologia , Feminino , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Masculino , Distribuição Aleatória , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia , Desmame
5.
Pathologe ; 41(3): 211-223, 2020 May.
Artigo em Alemão | MEDLINE | ID: mdl-32253499

RESUMO

The gut is the largest immune organ of the human body with an enormous mucosal interface. By acting as a physical barrier and by hosting many of the body's immune cells and tissues, the gut is the first line of defense against potentially harmful substances. Therefore, diseases leading to impaired immune response or disruption of the epithelial barrier result in autoimmune, infectious, or inflammatory bowel disease, frequently associated with diarrhea, malabsorption, melena, and growth failure. The differential diagnosis represents an interdisciplinary challenge in this group of rare diseases. The diseases are characterized by clinical, immunological, and histopathological features caused by mutations in single genes. In the following, we will focus on histological findings within the various entities of immunodeficiencies.


Assuntos
Trato Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças da Imunodeficiência Primária/imunologia , Humanos , Imunidade Inata , Mucosa Intestinal , Membrana Mucosa
6.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32206781

RESUMO

Stress is a biological adaptive response to restore homeostasis, and occurs in every animal production system, due to the multitude of stressors present in every farm. Heat stress is one of the most common environmental challenges to poultry worldwide. It has been extensively demonstrated that heat stress negatively impacts the health, welfare, and productivity of broilers and laying hens. However, basic mechanisms associated with the reported effects of heat stress are still not fully understood. The adaptive response of poultry to a heat stress situation is complex and intricate in nature, and it includes effects on the intestinal tract. This review offers an objective overview of the scientific evidence available on the effects of the heat stress response on different facets of the intestinal tract of poultry, including its physiology, integrity, immunology, and microbiota. Although a lot of knowledge has been generated, many gaps persist. The development of standardized models is crucial to be able to better compare and extrapolate results. By better understanding how the intestinal tract is affected in birds subjected to heat stress conditions, more targeted interventions can be developed and applied.


Assuntos
Bem-Estar do Animal , Microbioma Gastrointestinal , Resposta ao Choque Térmico , Aves Domésticas/fisiologia , Animais , Fazendas , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Aves Domésticas/imunologia , Aves Domésticas/microbiologia
7.
Immunity ; 52(2): 241-255, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32075727

RESUMO

Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.


Assuntos
Asma/imunologia , Asma/microbiologia , Trato Gastrointestinal , Pulmão , Microbiota/imunologia , Animais , Asma/patologia , Asma/fisiopatologia , Disbiose/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/virologia , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/parasitologia , Pulmão/virologia , Sistema Respiratório/imunologia , Sistema Respiratório/microbiologia , Sistema Respiratório/parasitologia , Sistema Respiratório/virologia
9.
Arch Anim Nutr ; 74(4): 271-295, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32108496

RESUMO

Short and medium-chain fatty acids (SCFA and MCFA, respectively) are commonly used as feed additives in piglets to promote health and prevent post-weaning diarrhoea. Considering that the mechanism and site of action of these fatty acids can differ, a combined supplementation could result in a synergistic action. Considering this, it was aimed to assess the potential of two new in-feed additives based on butyrate or heptanoate, protected with sodium salts of MCFA from coconut distillates, against enterotoxigenic Escherichia coli (ETEC) F4+ using an experimental disease model. Two independent trials were performed in 48 early-weaned piglets fed a control diet (CTR) or a diet supplemented with MCFA-protected sodium butyrate (BUT+; Trial 1) or sodium heptanoate (HPT+; Trial 2). After 1 week of adaptation, piglets were challenged with a single oral inoculum of ETEC F4+ (minimum 1.4 · 109 cfu). One animal per pen was euthanised on days 4 and 8 post-inoculation (PI) and the following variables assessed: growth performance, clinical signs, gut fermentation, intestinal morphology, inflammatory mediators, pathogen excretion and colon microbiota. None of the additives recovered growth performance or reduced diarrhoea when compared to the respective negative controls. However, both elicited different responses against ETEC F4+. The BUT+ additive did not lead to reduce E. coli F4 colonisation but enterobacterial counts and goblet cell numbers in the ileum were increased on day 8 PI and this followed higher serum TNF-α concentrations on day 4 PI. The Firmicutes:Bacteroidetes ratio was nevertheless increased. Findings in the HPT+ treatment trial included fewer animals featuring E. coli F4 in the colon and reduced Enterobacteriaceae (determined by 16S RNA sequencing) on day 4 PI. In addition, while goblet cell numbers were lower on day 8 PI, total SCFA levels were reduced in the colon. Results indicate the efficacy of MCFA-protected heptanoate against ETEC F4+ and emphasise the potential trophic effect of MCFA-protected butyrate on the intestinal epithelium likely reinforcing the gut barrier.


Assuntos
Ácido Butírico/metabolismo , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/efeitos dos fármacos , Heptanoatos/metabolismo , Sus scrofa/fisiologia , Ração Animal/análise , Animais , Ácido Butírico/administração & dosagem , Cocos/química , Colo/efeitos dos fármacos , Colo/microbiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Escherichia coli Enterotoxigênica/fisiologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Ácidos Graxos/administração & dosagem , Fermentação/efeitos dos fármacos , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Heptanoatos/administração & dosagem , Masculino , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/microbiologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia
10.
Cytotherapy ; 22(3): 166-171, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32063474

RESUMO

Gastrointestinal (GI) tract is the most common site of extranodal involvement in non-Hodgkin lymphoma. Life-threatening complications of GI may occur because of tumor or chemotherapy. Chimeric antigen receptor (CAR) T-cell therapy has been successfully used to treat refractory/relapse B-cell lymphoma, however, little is known about the efficacy and safety of CAR-T cell therapy for GI lymphoma. Here, we reported the efficacy and safety of CAR-T cell therapy in 14 patients with relapsed/refractory aggressive B-cell lymphoma involving the GI tract. After a sequential anti-CD22/anti-CD19 CAR-T therapy, 10 patients achieved an objective response, and seven patients achieved a complete response. CAR transgene and B-cell aplasia persisted in the majority of patients irrespective of response status. Six patients with partial response or stable disease developed progressive disease; two patients lost target antigens. Cytokine release syndrome (CRS) and GI adverse events were generally mild and manageable. The most common GI adverse events were diarrhea (4/14), vomiting (3/14) and hemorrhage (2/14). No perforation occurred during follow-up. Infection is a severe complication in GI lymphoma. Two patients were infected with bacteria that are able to colonize at GI; one died of sepsis early after CAR-T cells infusion. In conclusion, our study showed promising efficacy and safety of CAR-T cell therapy in refractory/relapsed B-cell lymphoma involving the GI tract. However, the characteristics of CAR-T-related infection in GI lymphoma should be further clarified to prevent and control infection.


Assuntos
Antígenos CD19/imunologia , Trato Gastrointestinal/imunologia , Imunoterapia Adotiva/efeitos adversos , Linfoma de Células B/imunologia , Linfoma de Células B/terapia , Receptores de Antígenos Quiméricos/metabolismo , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Linfócitos B/imunologia , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Receptores de Antígenos de Linfócitos T/imunologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Resultado do Tratamento
11.
Nat Rev Gastroenterol Hepatol ; 17(5): 263-278, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32103203

RESUMO

The human gastrointestinal tract is colonized by trillions of microorganisms that interact with the host to maintain structural and functional homeostasis. Acting as the interface between the site of the highest microbial burden in the human body and the richest immune compartment, a single layer of intestinal epithelial cells specializes in nutrient absorption, stratifies microorganisms to limit colonization of tissues and shapes the responses of the subepithelial immune cells. In this Review, we focus on the expression, regulation and functions of Toll-like receptors (TLRs) in the different intestinal epithelial lineages to analyse how epithelial recognition of bacteria participates in establishing homeostasis in the gut. In particular, we elaborate on the involvement of epithelial TLR signalling in controlling crypt dynamics, enhancing epithelial barrier integrity and promoting immune tolerance towards the gut microbiota. Furthermore, we comment on the regulatory mechanisms that fine-tune TLR-driven immune responses towards pathogens and revisit the role of TLRs in epithelial repair after injury. Finally, we discuss how dysregulation of epithelial TLRs can lead to the generation of dysbiosis, thereby increasing susceptibility to colitis and tumorigenesis.


Assuntos
Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Mucosa Intestinal/imunologia , Receptores Toll-Like/imunologia , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Trato Gastrointestinal/microbiologia , Homeostase , Humanos , Mucosa Intestinal/microbiologia
13.
Nat Commun ; 11(1): 252, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937752

RESUMO

Differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells are strictly controlled by T-cell receptor (TCR) signals; however, molecular mechanisms that govern these processes are incompletely understood. Here we show that Bach2 is an important regulator of Treg cell differentiation and homeostasis downstream of TCR signaling. Bach2 prevents premature differentiation of fully suppressive effector Treg (eTreg) cells, limits IL-10 production and is required for the development of peripherally induced Treg (pTreg) cells in the gastrointestinal tract. Bach2 attenuates TCR signaling-induced IRF4-dependent Treg cell differentiation. Deletion of IRF4 promotes inducible Treg cell differentiation and rescues pTreg cell differentiation in the absence of Bach2. In turn, loss of Bach2 normalizes eTreg cell differentiation of IRF4-deficient Treg cells. Mechanistically, Bach2 counteracts the DNA-binding activity of IRF4 and limits chromatin accessibility, thereby attenuating IRF4-dependent transcription. Thus, Bach2 balances TCR signaling induced transcriptional activity of IRF4 to maintain homeostasis of thymically-derived and peripherally-derived Treg cells.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Animais , Fatores de Transcrição de Zíper de Leucina Básica/deficiência , Diferenciação Celular/imunologia , Cromatina/metabolismo , Colite/imunologia , Modelos Animais de Doenças , Epigênese Genética/imunologia , Fatores de Transcrição Forkhead/metabolismo , Trato Gastrointestinal/imunologia , Regulação da Expressão Gênica/imunologia , Homeostase/imunologia , Fatores Reguladores de Interferon/deficiência , Fatores Reguladores de Interferon/metabolismo , Interleucina-10/biossíntese , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Transdução de Sinais/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
14.
Genome Biol ; 21(1): 6, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31948474

RESUMO

BACKGROUND: Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the Drosophila Genetic Reference Panel (DGRP) that resistance to infection is highly heritable, but our understanding of how the effects of genetic variants affect different molecular mechanisms to determine gut immunocompetence is still limited. RESULTS: To address this, we perform a systems genetics analysis of the gut transcriptomes from 38 DGRP lines that were orally infected with Pseudomonas entomophila. We identify a large number of condition-specific, expression quantitative trait loci (local-eQTLs) with infection-specific ones located in regions enriched for FOX transcription factor motifs. By assessing the allelic imbalance in the transcriptomes of 19 F1 hybrid lines from a large round robin design, we independently attribute a robust cis-regulatory effect to only 10% of these detected local-eQTLs. However, additional analyses indicate that many local-eQTLs may act in trans instead. Comparison of the transcriptomes of DGRP lines that were either susceptible or resistant to Pseudomonas entomophila infection reveals nutcracker as the only differentially expressed gene. Interestingly, we find that nutcracker is linked to infection-specific eQTLs that correlate with its expression level and to enteric infection susceptibility. Further regulatory analysis reveals one particular eQTL that significantly decreases the binding affinity for the repressor Broad, driving differential allele-specific nutcracker expression. CONCLUSIONS: Our collective findings point to a large number of infection-specific cis- and trans-acting eQTLs in the DGRP, including one common non-coding variant that lowers enteric infection susceptibility.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/microbiologia , Proteínas F-Box/genética , Alelos , Animais , Sítios de Ligação , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/imunologia , Drosophila melanogaster/metabolismo , Proteínas F-Box/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Polimorfismo de Nucleotídeo Único , Pseudomonas , Locos de Características Quantitativas , Elementos Reguladores de Transcrição , Transcriptoma
15.
Vet Immunol Immunopathol ; 221: 110009, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945652

RESUMO

A 14-day experiment was conducted to explore the pathological process and immune response of soybean meal (SBM) induced enteritis (SBMIE) in grass carp (Ctenopharyngodon idellus). The complete replacement of dietary fish meal (FM) with SBM resulted in a remarkable reduction in final body weight, weight gain ratio, and feed conversion efficiency (p < 0.05). The typical histopathological changes of SBMIE appeared starting at day 4, and progressively increased in severity until day 8, then gradually subsided after day 11. The course of SBMIE could be divided into incubation period (days 1-2), prodromal period (days 3-6), symptomatic period (days 7-10), and convalescent period (days 11-14). Transcription levels of pro-inflammatory cytokines, including IL-1ß, TNF-α, IL-6, IL-8, IL-17A/F1 and IFN-γ2, were up-regulated during the prodromal period, and then down-regulated during the convalescent period. Transcript levels of anti-inflammatory cytokines (IL-10 and TGFß1) and their receptors (IL-10R1 and TßRII), were up-regulated during the prodromal and convalescent periods. Transcript levels of MHCIIß, Igµ, Igτ, TCRδ, TCRß, CD4, and CD8α were altered in SBMIE. Furthermore, expression levels of T-bet, IFN-γ2, RORγ2 and IL-17A/F1 were significantly increased in the initiation of enteritis, whereas the transcript levels of Foxp3 and IL-2/15Ra were significantly up-regulated in the repair of enteritis. In conclusion, grass carp SBMIE is regulated by the adjustment of SBM-based diet intake, and the changes of the above-mentioned genes expression suggest that these genes may be involved in SBMIE.


Assuntos
Ração Animal/análise , Carpas/imunologia , Citocinas/imunologia , Enterite/veterinária , Doenças dos Peixes/imunologia , Trato Gastrointestinal/imunologia , Soja/efeitos adversos , Animais , Carpas/metabolismo , Citocinas/genética , Suplementos Nutricionais , Enterite/induzido quimicamente , Enterite/imunologia , Doenças dos Peixes/induzido quimicamente , Trato Gastrointestinal/patologia , Inflamação/genética , Soja/química
17.
Gut ; 69(1): 42-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036757

RESUMO

BACKGROUND AND AIMS: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome. METHODS: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines. RESULTS: Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon. CONCLUSION: Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.


Assuntos
Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Complicações na Gravidez/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Imunidade Adaptativa , Adulto , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Disbiose/imunologia , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Feminino , Seguimentos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Vida Livre de Germes , Humanos , Recém-Nascido , Doenças Inflamatórias Intestinais/imunologia , Masculino , Troca Materno-Fetal , Gravidez , Complicações na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Estudos Prospectivos
18.
Blood ; 135(8): 568-581, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31880771

RESUMO

Gastrointestinal (GI) tract involvement is the major cause of morbidity and mortality in acute graft-versus-host disease (GVHD), and pathological damage is largely attributable to inflammatory cytokine production. Recently, granulocyte-macrophage colony stimulating factor (GM-CSF) has been identified as a cytokine that mediates inflammation in the GI tract, but the transcriptional program that governs GM-CSF production and the mechanism by which GM-CSF links adaptive to innate immunity within this tissue site have not been defined. In the current study, we identified Bhlhe40 as a key transcriptional regulator that governs GM-CSF production by CD4+ T cells and mediates pathological damage in the GI tract during GVHD. In addition, we observed that GM-CSF was not regulated by either interleukin 6 (IL-6) or IL-23, which are both potent inducers of GVHD-induced colonic pathology, indicating that GM-CSF constitutes a nonredundant inflammatory pathway in the GI tract. Mechanistically, GM-CSF had no adverse effect on regulatory T-cell reconstitution, but linked adaptive to innate immunity by enhancing the activation of donor-derived dendritic cells in the colon and subsequent accumulation of these cells in the mLNs. In addition, GM-CSF promoted indirect alloantigen presentation, resulting in the accumulation of donor-derived T cells with a proinflammatory cytokine phenotype in the colon. Thus, Bhlhe40+ GM-CSF+ CD4+ T cells constitute a colitogenic T-cell population that promotes indirect alloantigen presentation and pathological damage within the GI tract, positioning GM-CSF as a key regulator of GVHD in the colon and a potential therapeutic target for amelioration of this disease.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Antígenos CD4/imunologia , Linfócitos T CD4-Positivos/patologia , Doença Enxerto-Hospedeiro/patologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Proteínas de Homeodomínio/imunologia , Isoantígenos/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Colo/imunologia , Colo/patologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Doença Enxerto-Hospedeiro/imunologia , Camundongos Endogâmicos C57BL
19.
Inflamm Bowel Dis ; 26(1): 11-20, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31560044

RESUMO

Host sensing in the gut microbiota has been crucial in the regulation of intestinal homeostasis. Although inflammatory bowel diseases (IBDs), multifactorial chronic inflammatory conditions of the gastrointestinal tract, have been associated with intestinal dysbiosis, the detailed interactions between host and gut microbiota are still not completely understood. Enteroendocrine cells (EECs) represent 1% of the intestinal epithelium. Accumulating evidence indicates that EECs are key sensors of gut microbiota and/or microbial metabolites. They can secrete cytokines and peptide hormones in response to microbiota, either in traditional endocrine regulation or by paracrine impact on proximal tissues and/or cells or via afferent nerve fibers. Enteroendocrine cells also play crucial roles in mucosal immunity, gut barrier function, visceral hyperalgesia, and gastrointestinal (GI) motility, thereby regulating several GI diseases, including IBD. In this review, we will focus on EECs in sensing microbiota, correlating enteroendocrine perturbations with IBD, and the underlying mechanisms.


Assuntos
Células Enteroendócrinas/imunologia , Células Enteroendócrinas/microbiologia , Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Animais , Disbiose/imunologia , Disbiose/microbiologia , Gastroenteropatias/imunologia , Gastroenteropatias/microbiologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Homeostase/imunologia , Humanos , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia
20.
Gastroenterology ; 158(1): 95-110, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626754

RESUMO

Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy.


Assuntos
Gastroenteropatias/diagnóstico , Hepatopatias/diagnóstico , Biomarcadores/metabolismo , Gastroenteropatias/mortalidade , Gastroenteropatias/terapia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Glicômica , Glicosilação/efeitos dos fármacos , Humanos , Fígado/imunologia , Fígado/metabolismo , Hepatopatias/mortalidade , Hepatopatias/terapia , Polissacarídeos/metabolismo , Prognóstico , Proteômica , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo
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