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1.
Front Immunol ; 15: 1379798, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756777

RESUMO

Introduction: Cryptosporidiosis is a poorly controlled zoonosis caused by an intestinal parasite, Cryptosporidium parvum, with a high prevalence in livestock (cattle, sheep, and goats). Young animals are particularly susceptible to this infection due to the immaturity of their intestinal immune system. In a neonatal mouse model, we previously demonstrated the importance of the innate immunity and particularly of type 1 conventional dendritic cells (cDC1) among mononuclear phagocytes (MPs) in controlling the acute phase of C. parvum infection. These immune populations are well described in mice and humans, but their fine characterization in the intestine of young ruminants remained to be further explored. Methods: Immune cells of the small intestinal Peyer's patches and of the distal jejunum were isolated from naive lambs and calves at different ages. This was followed by their fine characterization by flow cytometry and transcriptomic analyses (q-RT-PCR and single cell RNAseq (lamb cells)). Newborn animals were infected with C. parvum, clinical signs and parasite burden were quantified, and isolated MP cells were characterized by flow cytometry in comparison with age matched control animals. Results: Here, we identified one population of macrophages and three subsets of cDC (cDC1, cDC2, and a minor cDC subset with migratory properties) in the intestine of lamb and calf by phenotypic and targeted gene expression analyses. Unsupervised single-cell transcriptomic analysis confirmed the identification of these four intestinal MP subpopulations in lamb, while highlighting a deeper diversity of cell subsets among monocytic and dendritic cells. We demonstrated a weak proportion of cDC1 in the intestine of highly susceptible newborn lambs together with an increase of these cells within the first days of life and in response to the infection. Discussion: Considering cDC1 importance for efficient parasite control in the mouse model, one may speculate that the cDC1/cDC2 ratio plays also a key role for the efficient control of C. parvum in young ruminants. In this study, we established the first fine characterization of intestinal MP subsets in young lambs and calves providing new insights for comparative immunology of the intestinal MP system across species and for future investigations on host-Cryptosporidium interactions in target species.


Assuntos
Criptosporidiose , Cryptosporidium parvum , Homeostase , Animais , Criptosporidiose/imunologia , Criptosporidiose/parasitologia , Cryptosporidium parvum/imunologia , Ovinos , Bovinos , Homeostase/imunologia , Células Dendríticas/imunologia , Células Dendríticas/parasitologia , Fagócitos/imunologia , Fagócitos/parasitologia , Animais Recém-Nascidos , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/imunologia , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/parasitologia , Macrófagos/imunologia , Macrófagos/parasitologia , Intestinos/parasitologia , Intestinos/imunologia , Ruminantes/parasitologia , Ruminantes/imunologia
2.
Sci Immunol ; 9(95): eadi5374, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758808

RESUMO

The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti-PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.


Assuntos
Microbioma Gastrointestinal , Imunoterapia , Macrófagos , Glicoproteínas de Membrana , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1 , Receptores Imunológicos , Animais , Receptores Imunológicos/imunologia , Receptores Imunológicos/deficiência , Receptores Imunológicos/genética , Camundongos , Microbioma Gastrointestinal/imunologia , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Macrófagos/imunologia , Inibidores de Checkpoint Imunológico/farmacologia , Camundongos Knockout , Feminino , Intestinos/imunologia
3.
Front Immunol ; 15: 1394501, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774883

RESUMO

Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that carry bioactive molecules. Among EVs, outer membrane vesicles (OMVs), specifically produced by Gram-negative bacteria, have been extensively characterized and their potential as vaccines, adjuvants or immunotherapeutic agents, broadly explored in mammals. Nonetheless, Gram-positive bacteria can also produce bilayered spherical structures from 20 to 400 nm involved in pathogenesis, antibiotic resistance, nutrient uptake and nucleic acid transfer. However, information regarding their immunomodulatory potential is very scarce, both in mammals and fish. In the current study, we have produced EVs from the Gram-positive probiotic Bacillus subtilis and evaluated their immunomodulatory capacities using a rainbow trout intestinal epithelial cell line (RTgutGC) and splenic leukocytes. B. subtilis EVs significantly up-regulated the transcription of several pro-inflammatory and antimicrobial genes in both RTgutGC cells and splenocytes, while also up-regulating many genes associated with B cell differentiation in the later. In concordance, B. subtilis EVs increased the number of IgM-secreting cells in splenocyte cultures, while at the same time increased the MHC II surface levels and antigen-processing capacities of splenic IgM+ B cells. Interestingly, some of these experiments were repeated comparing the effects of B. subtilis EVs to EVs obtained from another Bacillus species, Bacillus megaterium, identifying important differences. The data presented provides evidence of the immunomodulatory capacities of Gram-positive EVs, pointing to the potential of B. subtilis EVs as adjuvants or immunostimulants for aquaculture.


Assuntos
Bacillus subtilis , Vesículas Extracelulares , Leucócitos , Oncorhynchus mykiss , Baço , Animais , Bacillus subtilis/imunologia , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Oncorhynchus mykiss/imunologia , Oncorhynchus mykiss/microbiologia , Baço/imunologia , Baço/citologia , Leucócitos/imunologia , Leucócitos/metabolismo , Probióticos/farmacologia , Linhagem Celular , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Imunomodulação , Intestinos/imunologia
4.
Fish Shellfish Immunol ; 149: 109600, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701991

RESUMO

Excess utilization of plant protein sources in animal feed has been found to adversely affect the antioxidant properties and immunity of animals. While the role of gut microbes in plant protein-induced inflammation has been identified in various models, the specific mechanisms regulating gut microbes in crustaceans remain unclear. Accordingly, this study was designed to investigate the effects of replacing fishmeal with soybean meal (SM) on the hepatopancreas antioxidant and immune capacities, and gut microbial functions of crayfish, as well as the potential microbial regulatory mechanisms. 750 crayfish (4.00 g) were randomly divided into five groups: SS0, SS25, SS50, SS75, and SS100, and fed diets with different levels of soybean meal substituted for fishmeal for six weeks. High SM supplementation proved detrimental to maintaining hepatopancreas health, as indicated by an increase in hemolymph MDA content, GPT, and GOT activities, the observed rupture of hepatopancreas cell basement membranes, along with the decreased number of hepatopancreatic F cells. Moreover, crayfish subjected to high SM diets experienced obvious inflammation in hepatopancreas, together with up-regulated mRNA expression levels of nfkb, alf, and tlr (p<0.05), whereas the lzm mRNA expression level exhibited the highest value in the SS25 group. Furthermore, hepatopancreas antioxidant properties highly attenuated by the level of dietary SM substitution levels, as evidenced by the observed increase in MDA content (p<0.05), decrease in GSH content (p<0.05), and inhabitation of SOD, CAT, GPx, and GST activities (p<0.05), along with down-regulated hepatopancreas cat, gpx, gst, and mmnsod mRNA expression levels via inhibiting nrf2/keap1 pathway. Functional genes contributing to metabolism identified that high SM diets feeding significantly activated lipopolysaccharide biosynthesis, revealing gut dysfunction acted as the cause of inflammation. The global microbial co-occurrence network further indicated that the microbes contributing more to serum indicators and immunity were in module eigengene 17 (ME17). A structural equation model revealed that the genes related to alf directly drove the serum enzyme activities through microbes in ME17, with OTU399 and OTU533 identified as major biomarkers and classified into Proteobacteria that secrete endotoxins. To conclude, SM could replace 25 % of fishmeal in crayfish diets without negatively affecting immunity, and antioxidant capacity. Excessive SM levels contributed to gut dysfunction and weakened the innate immune system of crayfish.


Assuntos
Ração Animal , Antioxidantes , Astacoidea , Dieta , Microbioma Gastrointestinal , Glycine max , Hepatopâncreas , Animais , Astacoidea/imunologia , Astacoidea/genética , Ração Animal/análise , Glycine max/química , Antioxidantes/metabolismo , Dieta/veterinária , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopâncreas/imunologia , Hepatopâncreas/metabolismo , Imunidade Inata/efeitos dos fármacos , Distribuição Aleatória , Intestinos/imunologia , Intestinos/efeitos dos fármacos , Suplementos Nutricionais/análise
5.
Front Immunol ; 15: 1373876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715602

RESUMO

Objective: The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage polarization. Methods: A sepsis model was established using cecal ligation and puncture (CLP) to assess the effectiveness of EA. The extent of pathological injury was evaluated using Chiu's score, the expression of ZO-1 and Ocludin, and the impact on macrophage polarization was examined through flow cytometry and immunofluorescence staining. The expression of spermidine, one type of polyamine, and ornithine decarboxylase (ODC) was measured using ELISA and PCR. Once the efficacy was determined, a polyamine depletion model was created, and the role of polyamines was reassessed by evaluating efficacy and observing macrophage polarization. Results: EA treatment reduced the Chiu's score and increased the expression of ZO-1 and Ocludin in the intestinal tissue of septic mice. It inhibited the secretion of IL-1ß and TNF-α, promoted the polarization of M2-type macrophages, increased the secretion of IL-10, and upregulated the expression of Arg-1, spermidine, and ODC. However, after depleting polyamines, the beneficial effects of EA on alleviating intestinal tissue damage and modulating macrophage polarization disappeared. Conclusion: The mechanism underlying the alleviation of intestinal injury associated with CLP-induced sepsis by EA involves with the promotion of M2-type macrophage polarization mediated by spermidine expression.


Assuntos
Modelos Animais de Doenças , Eletroacupuntura , Macrófagos , Poliaminas , Sepse , Animais , Sepse/terapia , Sepse/metabolismo , Sepse/imunologia , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Eletroacupuntura/métodos , Poliaminas/metabolismo , Masculino , Ativação de Macrófagos , Intestinos/patologia , Intestinos/imunologia , Camundongos Endogâmicos C57BL , Citocinas/metabolismo
6.
Adv Parasitol ; 124: 1-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38754926

RESUMO

Intestinal trematodes constitute a major group of helminths that parasitize humans and animals with relevant morbidity and mortality. Despite the importance of the intestinal trematodes in medical and veterinary sciences, immunology and pathology of these helminth infections have been neglected for years. Apart from the work focused on the members of the family Echnistomatidae, there are only very isolated and sporadic studies on the representatives of other families of digeneans, which makes a compilation of all these studies necessary. In the present review, the most salient literature on the immunology and pathology of intestinal trematodes in their definitive hosts in examined. Emphasis will be placed on members of the echinostomatidae family, since it is the group in which the most work has been carried out. However, we also review the information on selected species of the families Brachylaimidae, Diplostomidae, Gymnophallidae, and Heterophyidae. For most of these families, coverage is considered under the following headings: (i) Background; (ii) Pathology of the infection; (iii) Immunology of the infection; and (iv) Human infections.


Assuntos
Enteropatias Parasitárias , Trematódeos , Infecções por Trematódeos , Animais , Humanos , Trematódeos/fisiologia , Trematódeos/imunologia , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/imunologia , Infecções por Trematódeos/veterinária , Enteropatias Parasitárias/imunologia , Enteropatias Parasitárias/parasitologia , Intestinos/parasitologia , Intestinos/patologia , Intestinos/imunologia , Interações Hospedeiro-Parasita/imunologia
8.
Food Funct ; 15(8): 4552-4563, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38584501

RESUMO

The exploration of edible insects, specifically Alphitobius diaperinus and Tenebrio molitor, as sustainable sources of protein for human consumption is an emerging field. However, research into their effects on intestinal health, especially in relation to inflammation and permeability, remains limited. Using ex vivo and in vivo models of intestinal health and disease, in this study we assess the impact of the above insects on intestinal function by focusing on inflammation, barrier dysfunction and morphological changes. Initially, human intestinal explants were exposed to in vitro-digested extracts of these insects, almond and beef. Immune secretome analysis showed that the inflammatory response to insect-treated samples was comparatively lower than it was for samples exposed to almond and beef. Animal studies using yellow mealworm (Tenebrio molitor) and buffalo (Alphitobius diaperinus) flours were then used to evaluate their safety in healthy rats and LPS-induced intestinal dysfunction rats. Chronic administration of these insect-derived flours showed no adverse effects on behavior, metabolism, intestinal morphology or immune response (such as inflammation or allergy markers) in healthy Wistar rats. Notably, in rats subjected to proinflammatory LPS-induced intestinal dysfunction, T. molitor consumption did not exacerbate symptoms, nor did it increase allergic responses. These findings validate the safety of these edible insects under healthy conditions, demonstrate their innocuity in a model of intestinal dysfunction, and underscore their promise as sustainable and nutritionally valuable dietary protein sources.


Assuntos
Insetos Comestíveis , Proteínas de Insetos , Ratos Wistar , Tenebrio , Animais , Ratos , Humanos , Masculino , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Enteropatias , Modelos Animais de Doenças , Feminino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos
9.
Nutrients ; 16(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38674840

RESUMO

Throughout infancy, IgA is crucial for maintaining gut mucosal immunity. This study aims to determine whether supplementing newborn mice with eight different strains of Bifidobacterium longum subsp. infantis might regulate their IgA levels. The strains were gavaged to BALB/C female (n = 8) and male (n = 8) dams at 1-3 weeks old. Eight strains of B. longum subsp. infantis had strain-specific effects in the regulation of intestinal mucosal barriers. B6MNI, I4MI, and I10TI can increase the colonic IgA level in females and males. I8TI can increase the colonic IgA level in males. B6MNI was also able to significantly increase the colonic sIgA level in females. B6MNI, I4MI, I8TI, and I10TI regulated colonic and Peyer's patch IgA synthesis genes but had no significant effect on IgA synthesis pathway genes in the jejunum and ileum. Moreover, the variety of sIgA-coated bacteria in male mice was changed by I4MI, I5TI, I8TI, and B6MNI. These strains also can decrease the relative abundance of Escherichia coli. These results indicate that B. longum subsp. infantis can promote IgA levels but show strain specificity. Different dietary habits with different strains of Bifidobacterium may have varying effects on IgA levels when supplemented in early infancy.


Assuntos
Bifidobacterium longum subspecies infantis , Bifidobacterium , Imunoglobulina A , Mucosa Intestinal , Camundongos Endogâmicos BALB C , Probióticos , Animais , Feminino , Masculino , Imunoglobulina A/metabolismo , Camundongos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Probióticos/administração & dosagem , Microbioma Gastrointestinal , Animais Recém-Nascidos , Intestinos/microbiologia , Intestinos/imunologia , Imunidade nas Mucosas , Especificidade da Espécie , Colo/microbiologia , Colo/imunologia , Colo/metabolismo , Imunoglobulina A Secretora/metabolismo
10.
Vet Immunol Immunopathol ; 271: 110753, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608406

RESUMO

Porcine epidemic diarrhea virus (PEDV) causes immensely large economic losses worldwide in the swine industry. PEDV attacks the intestine, disrupts intestinal epithelium morphology and barrier integrity, and results in profound diarrhea and high mortality. A commercially available isotonic protein solution (IPS) (Tonisity Px) has anecdotally been reported to be effective in supportive treatment of piglets with active PEDV infections. This study evaluated the effects of supplementing (or not) the drinking water of 14 day old PEDV-infected piglets with the IPS on the content of E-cadherin, fibronectin, interferon-alpha (IFN-α), and matrix metalloproteinase 9 (MMP-9) in duodenal tissue. The content of PEDV DNA in feces was also measured. Though both groups had similar PEDV shedding at day 1, IPS piglets had significantly lower PEDV shedding at day 5, 14 and 21. The IPS group also had a shorter duration of PEDV virus shedding. Levels of E-cadherin and fibronectin, both of which are structural proteins in the intestine, remained unchanged from baseline in the IPS group, whereas the same molecules decreased significantly in the control group. IFN-α, an antiviral cytokine, and MMP-9, an enzyme that aids in tissue remodeling, were increased at days 5 and 14 post infection, and then decreased at day 21 post-infection in the IPS group compared to control. Overall, the IPS used in this study enhanced epithelial intercellular adhesion (E-cadherin) and extracellular matrix structure (fibronectin), resulted in significantand favorable changes in MMP-9 activity, and favorably modulated IFN-α production. This is the first report of this panel of biomarkers, especially MMP-9 and IFN-α, in the face of in vivo PEDV infection. This is also the first report to investigate a commercially available swine product that does not need to be administered in solid feed, and that is already registered for use throughout Asia, Europe, South America, and North America. Overall, the results of this study serve to clarify the behavior of 4 key biomarkers in the presence of in vivo PEDV infection. The results also indicate that IPS (Tonisity Px) supplementation is a viable intervention to modulate the porcine intestinal immune response with favorable effects on the intestine.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Eliminação de Partículas Virais , Animais , Suínos , Vírus da Diarreia Epidêmica Suína/fisiologia , Vírus da Diarreia Epidêmica Suína/imunologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Doenças dos Suínos/virologia , Doenças dos Suínos/imunologia , Fibronectinas/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Caderinas/metabolismo , Intestinos/imunologia , Intestinos/virologia , Interferon-alfa/imunologia , Adesão Celular , Mucosa Intestinal/imunologia
11.
Food Funct ; 15(9): 4862-4873, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38587236

RESUMO

Intestinal infections are strongly associated with infant mortality, and intestinal immunoglobulin A (IgA) is important to protect infants from intestinal infections after weaning. This study aims to screen probiotics that can promote the production of intestinal IgA after weaning and further explore their potential mechanisms of action. In this study, probiotics promoting intestinal IgA production were screened in weanling mouse models. The results showed that oral administration of Bifidobacterium bifidum (B. bifidum) FL228.1 and Bifidobacterium bifidum (B. bifidum) FL276.1 significantly enhanced IgA levels in the small intestine and upregulated the expression of a proliferation-inducing ligand (APRIL) and its upstream regulatory factor toll-like receptor 4 (TLR4). Furthermore, B. bifidum FL228.1 upregulated the relative abundance of Lactobacillus, while B. bifidum FL276.1 increased the relative abundance of Marvinbryantia and decreased Mucispirillum, further elevating intestinal IgA levels. In summary, B. bifidum FL228.1 and B. bifidum FL276.1 can induce IgA production in the intestinal tract of weanling mice by promoting intestinal APRIL expression and mediating changes in the gut microbiota, thus playing a significant role in enhancing local intestinal immunity in infants.


Assuntos
Bifidobacterium bifidum , Microbioma Gastrointestinal , Imunoglobulina A , Probióticos , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Animais , Probióticos/farmacologia , Probióticos/administração & dosagem , Camundongos , Bifidobacterium bifidum/fisiologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Desmame , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Masculino , Intestinos/imunologia , Intestinos/microbiologia , Feminino , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Camundongos Endogâmicos BALB C
12.
Dev Comp Immunol ; 156: 105176, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38582249

RESUMO

Due to the ongoing global warming, the risk of heatwaves in the oceans is continuously increasing while our understanding of the physiological response of Litopenaeus vannamei under extreme temperature conditions remains limited. Therefore, this study aimed to evaluate the physiological responses of L. vannamei under heat stress. Our results indicated that as temperature rose, the structure of intestinal and hepatopancreatic tissues was damaged sequentially. Activity of immune-related enzymes (acid phosphatase/alkaline phosphatase) initially increased before decreased, while antioxidant enzymes (superoxide dismutase and glutathione-S transferase) activity and malondialdehyde content increased with rising temperature. In addition, the total antioxidant capacity decreased with rising temperature. With the rising temperature, there was a significant increase in the expression of caspase-3, heat shock protein 70, lipopolysaccharide-induced tumor necrosis factor-α, transcriptional enhanced associate domain and yorkie in intestinal and hepatopancreatic tissues. Following heat stress, the number of potentially beneficial bacteria (Rhodobacteraceae and Gemmonbacter) increased which maintain balance and promote vitamin synthesis. Intestinal transcriptome analysis revealed 852 differentially expressed genes in the heat stress group compared with the control group. KEGG functional annotation results showed that the endocrine system was the most abundant in Organismal systems followed by the immune system. These results indicated that heat stress leads to tissue damage in shrimp, however the shrimp may respond to stress through a coordinated interaction strategy of the endocrine system, immune system and gut microbiota. This study revealed the response mechanism of L. vannamei to acute heat stress and potentially provided a theoretical foundation for future research on shrimp environmental adaptations.


Assuntos
Microbioma Gastrointestinal , Resposta ao Choque Térmico , Penaeidae , Transcriptoma , Animais , Penaeidae/imunologia , Penaeidae/microbiologia , Penaeidae/genética , Resposta ao Choque Térmico/genética , Resposta ao Choque Térmico/imunologia , Microbioma Gastrointestinal/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Sistema Imunitário/metabolismo , Sistema Imunitário/imunologia , Perfilação da Expressão Gênica , Hepatopâncreas/imunologia , Hepatopâncreas/metabolismo , Proteínas de Artrópodes/metabolismo , Proteínas de Artrópodes/genética , Antioxidantes/metabolismo
13.
World J Gastroenterol ; 30(15): 2096-2108, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38681982

RESUMO

Probiotics are live microorganisms exerting beneficial effects on the host's health when administered in adequate amounts. Among the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae, Bifidobacteriaceae and yeasts. Most of them have been shown, both in vitro and in vivo studies of intestinal inflammation models, to provide favorable results by means of improving the gut microbiota composition, promoting the wound healing process and shaping the immunological responses. Chronic intestinal conditions, such as inflammatory bowel diseases (IBD), are characterized by an imbalance in microbiota composition, with decreased diversity, and by relapsing and persisting inflammation, which may lead to mucosal damage. Although the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial, it is without doubt that these microorganisms and their metabolites, now named postbiotics, have a positive influence on both the host's microbiota and the immune system, and ultimately alter the topical tissue microenvironment. This influence is achieved through three axes: (1) By displacement of potential pathogens via competitive exclusion; (2) by offering protection to the host through the secretion of various defensive mediators; and (3) by supplying the host with essential nutrients. We will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses, highlighting which species are the most beneficial against intestinal inflammation.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Probióticos , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Humanos , Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/terapia , Animais , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Intestinos/imunologia , Intestinos/microbiologia , Disbiose/imunologia
14.
ACS Biomater Sci Eng ; 10(5): 3387-3400, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38656158

RESUMO

Given the worldwide problem posed by enteric pathogens, the discovery of safe and efficient intestinal adjuvants combined with novel antigen delivery techniques is essential to the design of mucosal vaccines. In this work, we designed poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) to codeliver all-trans retinoic acid (atRA), novel antigens, and CpG. To address the insolubility of the intestinal adjuvant atRA, we utilized PLGA to encapsulate atRA and form a "nanocapsid" with polydopamine. By leveraging polydopamine, we adsorbed the water-soluble antigens and the TLR9 agonist CpG onto the NPs' surface, resulting in the pathogen-mimicking PLPCa NPs. In this study, the novel fusion protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis antigens HBHA, Ag85B, and Bfra, was coloaded onto the NPs. In vitro, PLPCa NPs were shown to promote the activation and maturation of bone marrow-derived dendritic cells. Additionally, we found that PLPCa NPs created an immune-rich microenvironment at the injection site following intramuscular administration. From the results, the PLPCa NPs induced strong IgA levels in the gut in addition to enhancing powerful systemic immune responses. Consequently, significant declines in the bacterial burden and inflammatory score were noted in PLPCa NPs-treated mice. In summary, PLPCa can serve as a novel and safe vaccine delivery platform against gut pathogens, such as paratuberculosis, capable of activating both systemic and intestinal immunity.


Assuntos
Nanopartículas , Paratuberculose , Animais , Nanopartículas/química , Paratuberculose/imunologia , Paratuberculose/prevenção & controle , Camundongos , Tretinoína/química , Tretinoína/farmacologia , Mycobacterium avium subsp. paratuberculosis/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/química , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Intestinos/imunologia , Intestinos/microbiologia , Camundongos Endogâmicos C57BL , Feminino , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/administração & dosagem , Vacinas Bacterianas/imunologia , Camundongos Endogâmicos BALB C
15.
J Nutr Biochem ; 129: 109634, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38561081

RESUMO

In two previous studies, we showed that supplementing a high-fat (HF) diet with 9% w/w U. dioica protects against fat accumulation, insulin resistance, and dysbiosis. This follow-up study in C57BL6/J mice aimed at testing: (i) the efficacy of the vegetable at lower doses: 9%, 4%, and 2%, (ii) the impact on intestinal T and B cell phenotype and secretions, (iii) impact on fat and glucose absorption during excess nutrient provision. At all doses, the vegetable attenuated HF diet induced fat accumulation in the mesenteric, perirenal, retroperitoneal fat pads, and liver but not the epididymal fat pad. The 2% dose protected against insulin resistance, prevented HF diet-induced decreases in intestinal T cells, and IgA+ B cells and activated T regulatory cells (Tregs) when included both in the LF and HF diets. Increased Tregs correlated with reduced inflammation; prevented increases in IL6, IFNγ, and TNFα in intestine but not expression of TNFα in epididymal fat pad. Testing of nutrient absorption was performed in enteroids. Enteroids derived from mice fed the HF diet supplemented with U. dioica had reduced absorption of free fatty acids and glucose compared to enteroids from mice fed the HF diet only. In enteroids, the ethanolic extract of U. dioica attenuated fat absorption and downregulated the expression of the receptor CD36 which facilitates uptake of fatty acids. In conclusion, including U. dioica in a HF diet, attenuates fat accumulation, insulin resistance, and inflammation. This is achieved by preventing dysregulation of immune homeostasis and in the presence of excess fat, reducing fat and glucose absorption.


Assuntos
Linfócitos B , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Urtica dioica , Animais , Dieta Hiperlipídica/efeitos adversos , Masculino , Obesidade/metabolismo , Urtica dioica/química , Linfócitos B/metabolismo , Linfócitos B/imunologia , Resistência à Insulina , Absorção Intestinal/efeitos dos fármacos , Camundongos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/efeitos dos fármacos , Nutrientes , Fenótipo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Verduras/química , Intestinos/efeitos dos fármacos , Intestinos/imunologia
16.
Int Immunopharmacol ; 133: 112058, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38613883

RESUMO

Fetal growth restriction (FGR) is a major cause of premature and low-weight births, which increases the risk of necrotizing enterocolitis (NEC); however, the association remains unclear. We report a close correlation between placental polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and NEC. Newborns with previous FGR exhibited intestinal inflammation and more severe NEC symptoms than healthy newborns. Placental PMN-MDSCs are vital regulators of fetal development and neonatal gut inflammation. Placental single-cell transcriptomics revealed that PMN-MDSCs populations and olfactomedin-4 gene (Olfm4) expression levels were significantly increased in PMN-MDSCs in later pregnancy compared to those in early pregnancy and non-pregnant females. Female mice lacking Olfm4 in myeloid cells mated with wild-type males showed FGR during pregnancy, with a decreased placental PMN-MDSCs population and expression of growth-promoting factors (GPFs) from placental PMN-MDSCs. Galectin-3 (Gal-3) stimulated the OLFM4-mediated secretion of GPFs by placental PMN-MDSCs. Moreover, GPF regulation via OLFM4 in placental PMN-MDSCs was mediated via hypoxia inducible factor-1α (HIF-1α). Notably, the offspring of mothers lacking Olfm4 exhibited intestinal inflammation and were susceptible to NEC. Additionally, OLFM4 expression decreased in placental PMN-MDSCs from pregnancies with FGR and was negatively correlated with neonatal morbidity. These results revealed that placental PMN-MDSCs contributed to fetal development and ameliorate newborn intestinal inflammation.


Assuntos
Retardo do Crescimento Fetal , Células Supressoras Mieloides , Placenta , Animais , Feminino , Gravidez , Humanos , Placenta/imunologia , Placenta/metabolismo , Recém-Nascido , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Retardo do Crescimento Fetal/imunologia , Camundongos , Camundongos Knockout , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Fator Estimulador de Colônias de Granulócitos/genética , Camundongos Endogâmicos C57BL , Masculino , Galectinas/metabolismo , Galectinas/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Intestinos/imunologia , Intestinos/patologia
17.
Fish Shellfish Immunol ; 149: 109551, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599363

RESUMO

The present study aimed to evaluate the effect of king oyster mushroom (Pleurotus eryngii) root waste and soybean meal co-fermented protein (CFP) on growth performance, feed utilization, immune status, hepatic and intestinal health of largemouth bass (Micropterus salmoides). Largemouth bass (12.33 ± 0.18 g) were divided into five groups, fed with diets containing 0 %, 5 %, 10 %, 15 % and 20 % CFP respectively for 7 weeks. The growth performance and dietary utilization were slightly improved by the supplementation of CFP. In addition, improved immunoglobulin M (IgM) content and lysozyme activity in treatments confirm the enhancement of immunity in fish by the addition of CFP, especially in fish fed 20 % CFP (P < 0.05). Furthermore, CFP significantly improved liver GSH (glutathione) content in groups D10 and D15 (P < 0.05), and slightly improved total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity while slightly reduced malondialdehyde (MDA) content. Simultaneously, the upregulation of lipolysis-related genes (PPARα, CPT1 and ACO) expression and downregulation of lipid synthesis-related genes (ACC and DGAT1) expression was recorded in the group D20 compared with the control (P < 0.05), which were consistent with the decreased liver lipid contents, suggests that lipid metabolism was improved by CFP. In terms of intestinal structural integrity, ameliorated intestinal morphology in treatments were consistent with the upregulated Occludin, Claudin-1 and ZO-1 genes expression. The intestinal pro-inflammatory cytokines (TNF-α and IL-8) expression were suppressed while the anti-inflammatory cytokines (IL-10 and TGF-ß) were activated in treatments. The expression of antimicrobial peptides (Hepcidin-1, Piscidin-2 and Piscidin-3) and intestinal immune effectors (IgM and LYZ) were slightly up-regulated in treatments. Additionally, the relative abundance of intestinal beneficial bacteria (Firmicutes) increased while the relative abundance of potential pathogenic bacteria (Fusobacterium and Proteobacteria) decreased, which indicated that the intestinal microbial community was well-reorganized by CFP. In conclusion, dietary CFP improves growth, immunity, hepatic and intestinal health of largemouth bass, these data provided a theoretical basis for the application of this novel functional protein ingredient in fish.


Assuntos
Ração Animal , Bass , Dieta , Suplementos Nutricionais , Glycine max , Fígado , Pleurotus , Animais , Bass/imunologia , Bass/crescimento & desenvolvimento , Ração Animal/análise , Dieta/veterinária , Pleurotus/química , Glycine max/química , Fígado/imunologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Suplementos Nutricionais/análise , Intestinos/imunologia , Intestinos/efeitos dos fármacos , Fermentação , Imunidade Inata/efeitos dos fármacos , Distribuição Aleatória , Raízes de Plantas/química , Relação Dose-Resposta a Droga
18.
Fish Shellfish Immunol ; 149: 109549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599365

RESUMO

The study was designed to investigate the effects of replacing fish oil by algal oil and rapeseed oil on histomorphology indices of the intestine, skin and gill, mucosal barrier status and immune-related genes of mucin and antimicrobial peptide (AMP) genes in Atlantic salmon (Salmo salar). For these purposes, Atlantic salmon smolts were fed three different diets. The first was a control diet containing fish oil but no Schizochytrium oil. In the second diet, almost 50 % of the fish oil was replaced with algal oil, and in the third diet, fish oil was replaced entirely with algal oil. The algal oil contained mostly docosahexaenoic acid (DHA) and some eicosapentaenoic acid (EPA). The study lasted for 49 days in freshwater (FW), after which some fish from each diet group were transferred to seawater (SW) for a 48-h challenge test at 33 ppt to test their ability to tolerate high salinity. Samples of skin, gills, and mid intestine [both distal (DI) and anterior (AI) portions of the mid intestine] were collected after the feeding trial in FW and after the SW-challenge test to assess the effects of the diets on the structure and immune functions of the mucosal surfaces. The results showed that the 50 % VMO (Veramaris® algal oil) dietary group had improved intestinal, skin, and gill structures. Principal component analysis (PCA) of the histomorphological parameters demonstrated a significant effect of the algal oil on the intestine, skin, and gills. In particular, the mucosal barrier function of the intestine, skin, and gills was enhanced in the VMO 50 % dietary group after the SW challenge, as evidenced by increased mucous cell density. Immunolabelling of heat shock protein 70 (HSP70) in the intestine (both DI and AI) revealed downregulation of the protein expression in the 50 % VMO group and a corresponding upregulation in the 100 % VMO group compared to 0 % VMO. The reactivity of HSP70 in the epithelial cells was higher after the SW challenge compared to the FW phase. Immune-related genes related to mucosal defense, such as mucin genes [muc2, muc5ac1 (DI), muc5ac1 (AI), muc5ac2, muc5b (skin), and muc5ac1 (gills)], and antimicrobial peptide genes [def3 (DI), def3 (AI), and cath1 (skin)] were significantly upregulated in the 50 % VMO group. PCA of gene expression demonstrated the positive influences on gene regulation in the 50 % VMO dietary group. In conclusion, this study demonstrated the positive effect of substituting 50 % of fish oil with algal oil in the diets of Atlantic salmon. The findings of histomorphometry, mucosal mapping, immunohistochemistry, and immune-related genes connected to mucosal responses all support this conclusion.


Assuntos
Ração Animal , Dieta , Óleo de Brassica napus , Salmo salar , Animais , Salmo salar/imunologia , Dieta/veterinária , Óleo de Brassica napus/química , Ração Animal/análise , Mucosa/imunologia , Óleos de Peixe/administração & dosagem , Pele/imunologia , Pele/efeitos dos fármacos , Estações do Ano , Brânquias/imunologia , Brânquias/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/imunologia
19.
Fish Shellfish Immunol ; 149: 109556, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38608848

RESUMO

Japanese eel, Anguilla japonica, holds significant importance in Taiwanese aquaculture. With the intensification of eel farming, the impact of Edwardsiella tarda has become increasingly severe. Consequently, the abusive use of antibiotics has risen. Bacillus subtilis natto NTU-18, a strain of Bacillus with a high survival rate in feed processing, plays a crucial role in promoting intestinal health through competitive rejection, enhancing immune responses against bacterial pathogens, and improving intestinal health by modulating gastrointestinal microbiota to produce beneficial metabolites of mice and grass carp, Ctenopharyngodon idella. This study investigated the effects of different proportions (control, 0.25 %, 0.5 %, 1 %, and 2 %) of B. subtilis natto NTU-18 added to paste feed on the growth performance, intestinal morphology, and microbiota, expression of immune-related genes, and resistance to E. tarda in Japanese glass eel. The results indicated that the growth performance of all groups with B. subtilis natto NTU-18 added was significantly higher than that of the control group and did not impact the villi morphology. The expression of immune-related genes in the kidney, specifically HSP70 and SOD, was significantly higher from 0.5 % and above than the control; however, no significant differences were observed in CAT, POD, and HSP90. In the liver, significant differences were found in HSP70 and IgM above 0.25 % compared to the control group, with no significant differences in SOD, CAT, POD, and HSP90 among all groups. Additionally, intestinal microbiota analysis revealed that the 2 % additional group had significantly lower diversity than other groups, with Cetobacterium as the dominant species. The challenge test observed that the survival rates of the 0.5 % and 1 % groups were significantly higher. This research suggests that adding 0.5 % and 1 % of B. subtilis natto NTU-18 to the diet is beneficial for Japanese glass eel's immunity, growth performance, and disease resistance.


Assuntos
Anguilla , Ração Animal , Bacillus subtilis , Dieta , Resistência à Doença , Doenças dos Peixes , Microbioma Gastrointestinal , Intestinos , Probióticos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Anguilla/imunologia , Anguilla/crescimento & desenvolvimento , Ração Animal/análise , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Dieta/veterinária , Probióticos/farmacologia , Probióticos/administração & dosagem , Intestinos/imunologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/veterinária , Edwardsiella tarda/fisiologia , Suplementos Nutricionais/análise , Imunidade Inata , Distribuição Aleatória
20.
World J Gastroenterol ; 30(14): 1963-1967, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38681124

RESUMO

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel. On the flip side, functions also arise from its role as an interface with the environment. Indeed, the gut houses microorganisms, collectively known as the gut microbiota, which interact with the host, and is the site of complex immune activities. Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut, especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems. This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.


Assuntos
Microbioma Gastrointestinal , Motilidade Gastrointestinal , Intestinos , Humanos , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Motilidade Gastrointestinal/fisiologia , Intestinos/microbiologia , Intestinos/imunologia , Intestinos/fisiopatologia , Inflamação/imunologia , Inflamação/fisiopatologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Animais
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