Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
1.
Front Immunol ; 14: 1188757, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180172

RESUMO

Rotavirus A (RVA) causes ~200,000 diarrheal deaths annually in children <5yrs, mostly in low- and middle-income countries. Risk factors include nutritional status, social factors, breastfeeding status, and immunodeficiency. We evaluated the effects of vitamin A (VA) deficiency/VA supplementation and RVA exposure (anamnestic) on innate and T cell immune responses in RVA seropositive pregnant and lactating sows and passive protection of their piglets post-RVA challenge. Sows were fed VA deficient (VAD) or sufficient (VAS) diets starting at gestation day (GD)30. A subset of VAD sows received VA supplementation from GD|76 (30,000IU/day, VAD+VA). Sows (6 groups) were inoculated with porcine RVA G5P[7] (OSU strain) or Minimal Essential Medium (mock) at GD~90: VAD+RVA; VAS+RVA; VAD+VA+RVA; VAD-mock; VAS-mock; and VAD+VA-mock. Blood, milk, and gut-associated tissues were collected from sows at several time points to examine innate [natural killer (NK), dendritic (DC) cells], T cell responses and changes in genes involved in the gut-mammary gland (MG)-immunological axis trafficking. Clinical signs of RVA were evaluated post inoculation of sows and post-challenge of piglets. We observed decreased frequencies of NK cells, total and MHCII+ plasmacytoid DCs, conventional DCs, CD103+ DCs and CD4+/CD8+ and T regulatory cells (Tregs) and NK cell activity in VAD+RVA sows. Polymeric Ig receptor and retinoic acid receptor alpha (RARα) genes were downregulated in mesenteric lymph nodes and ileum of VAD+RVA sows. Interestingly, RVA-specific IFN-γ producing CD4+/CD8+ T cells were increased in VAD-Mock sows, coinciding with increased IL-22 suggesting inflammation in these sows. VA supplementation to VAD+RVA sows restored frequencies of NK cells and pDCs, and NK activity, but not tissue cDCs and blood Tregs. In conclusion, similar to our recent observations of decreased B cell responses in VAD sows that led to decreased passive immune protection of their piglets, VAD impaired innate and T cell responses in sows, while VA supplementation to VAD sows restored some, but not all responses. Our data reiterate the importance of maintaining adequate VA levels and RVA immunization in pregnant and lactating mothers to achieve optimal immune responses, efficient function of the gut-MG-immune cell-axis and to improve passive protection of their piglets.


Assuntos
Infecções por Rotavirus , Rotavirus , Deficiência de Vitamina A , Gravidez , Suínos , Animais , Feminino , Vitamina A/farmacologia , Linfócitos T CD8-Positivos/metabolismo , Lactação , Suplementos Nutricionais , Imunidade
2.
Viruses ; 14(11)2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36366453

RESUMO

The aim of this study was to determine the impact of vitamin A deficiency (VAD)/supplementation (±VA) and group A RV (RVA) maternal immunization of RVA seropositive multiparous pregnant sows, on their immune responses (anamnestic response) and on passive protection of their piglets against RVA challenge. Our results showed that VAD- mock sows had increased RVA RNA shedding at 1-5 days post piglet RVA challenge, and their litters had increased RVA shedding and diarrhea frequency throughout the experiment. VAD decreased memory B cell frequencies while VA supplementation increased RVA specific IgA/IgG antibody (Ab) secreting cell (ASC) numbers in blood, milk, and tissues of RVA inoculated VAD sows. The increased numbers of RVA specific IgA/IgG ASCs in blood, milk/colostrum, intestinal contents, and tissues in VA supplemented VAD sows, suggest a role of VA in B cell immunity and trafficking to tissues. We also observed that RVA inoculated sows had the highest viral neutralizing Ab titers in serum and milk while VA supplementation of VAD sows and RVA inoculation increased IgA+ B cell frequencies in sow colostrum. In summary, we demonstrated that daily oral VA-supplementation (2nd trimester-throughout lactation) to RVA inoculated VAD sows improved the function of their gut-mammary-IgA immunological axis, reducing viral RNA shedding, diarrhea, and increasing weight gain in suckling piglets.


Assuntos
Rotavirus , Gravidez , Suínos , Animais , Feminino , Vitamina A , Imunidade Adaptativa , Leite , Imunoglobulina A , Suplementos Nutricionais , Diarreia/prevenção & controle
3.
mSphere ; 7(5): e0027022, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36073800

RESUMO

Human rotavirus (HRV) is a major cause of childhood diarrhea in developing countries where widespread malnutrition contributes to the decreased oral vaccine efficacy and increased prevalence of other enteric infections, which are major concerns for global health. Neonatal gnotobiotic (Gn) piglets closely resemble human infants in their anatomy, physiology, and outbred status, providing a unique model to investigate malnutrition, supplementations, and HRV infection. To understand the molecular signatures associated with immune enhancement and reduced diarrheal severity by Escherichia coli Nissle 1917 (EcN) and tryptophan (TRP), immunological responses and global nontargeted metabolomics and lipidomics approaches were investigated on the plasma and fecal contents of malnourished pigs transplanted with human infant fecal microbiota and infected with virulent (Vir) HRV. Overall, EcN + TRP combined (rather than individual supplement action) promoted greater and balanced immunoregulatory/immunostimulatory responses associated with greater protection against HRV infection and disease in malnourished humanized piglets. Moreover, EcN + TRP treatment upregulated the production of several metabolites with immunoregulatory/immunostimulatory properties: amino acids (N-acetylserotonin, methylacetoacetyl-CoA), lipids (gamma-butyrobetaine, eicosanoids, cholesterol-sulfate, sphinganine/phytosphingosine, leukotriene), organic compound (biliverdin), benzenoids (gentisic acid, aminobenzoic acid), and nucleotides (hypoxathine/inosine/xanthine, cytidine-5'-monophosphate). Additionally, the levels of several proinflammatory metabolites of organic compounds (adenosylhomocysteine, phenylacetylglycine, urobilinogen/coproporphyrinogen) and amino acid (phenylalanine) were reduced following EcN + TRP treatment. These results suggest that the EcN + TRP effects on reducing HRV diarrhea in neonatal Gn pigs were at least in part due to altered metabolites, those involved in lipid, amino acid, benzenoids, organic compounds, and nucleotide metabolism. Identification of these important mechanisms of EcN/TRP prevention of HRV diarrhea provides novel targets for therapeutics development. IMPORTANCE Human rotavirus (HRV) is the most common cause of viral gastroenteritis in children, especially in developing countries, where the efficacy of oral HRV vaccines is reduced. Escherichia coli Nissle 1917 (EcN) is used to treat enteric infections and ulcerative colitis while tryptophan (TRP) is a biomarker of malnutrition, and its supplementation can alleviate intestinal inflammation and normalize intestinal microbiota in malnourished hosts. Supplementation of EcN + TRP to malnourished humanized gnotobiotic piglets enhanced immune responses and resulted in greater protection against HRV infection and diarrhea. Moreover, EcN + TRP supplementation increased the levels of immunoregulatory/immunostimulatory metabolites while decreasing the production of proinflammatory metabolites in plasma and fecal samples. Profiling of immunoregulatory and proinflammatory biomarkers associated with HRV perturbations will aid in the identification of treatments against HRV and other enteric diseases in malnourished children.


Assuntos
Infecções por Escherichia coli , Transplante de Microbiota Fecal , Desnutrição , Infecções por Rotavirus , Triptofano , Animais , Humanos , Lactente , Aminobenzoatos , Biliverdina/metabolismo , Colesterol , Coenzima A/metabolismo , Coproporfirinogênios , Citidina/metabolismo , Diarreia , Escherichia coli/metabolismo , Vida Livre de Germes , Inosina/metabolismo , Lipídeos , Desnutrição/terapia , Desnutrição/complicações , Metaboloma , Microbiota , Nucleotídeos/metabolismo , Fenilalanina/metabolismo , Rotavirus , Sulfatos , Suínos , Triptofano/farmacologia , Urobilinogênio/metabolismo , Xantinas
4.
mSphere ; 6(2)2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789939

RESUMO

Human rotavirus (HRV) infection is a major cause of gastroenteritis in children worldwide. Broad-spectrum antibiotic-induced intestinal microbial imbalance and the ensuing immune-metabolic dysregulation contribute to the persistence of HRV diarrhea. Escherichia coli Nissle 1917 (EcN), a Gram-negative probiotic, was shown to be a potent immunostimulant and alleviated HRV-induced diarrhea in monocolonized gnotobiotic (Gn) piglets. Our goal was to determine how EcN modulates immune responses in ciprofloxacin (Cipro)-treated Gn piglets colonized with a defined commensal microbiota (DM) and challenged with virulent HRV (VirHRV). Cipro given in therapeutic doses for a short term reduced serum and intestinal total and HRV-specific antibody titers, while EcN treatment alleviated this effect. Similarly, EcN treatment increased the numbers of total immunoglobulin-secreting cells, HRV-specific antibody-secreting cells, activated antibody-forming cells, resting/memory antibody-forming B cells, and naive antibody-forming B cells in systemic and/or intestinal tissues. Decreased levels of proinflammatory but increased levels of immunoregulatory cytokines and increased frequencies of Toll-like receptor-expressing cells were evident in the EcN-treated VirHRV-challenged group. Moreover, EcN treatment increased the frequencies of T helper and T cytotoxic cells in systemic and/or intestinal tissues pre-VirHRV challenge and the frequencies of T helper cells, T cytotoxic cells, effector T cells, and T regulatory cells in systemic and/or intestinal tissues postchallenge. Moreover, EcN treatment increased the frequencies of systemic and mucosal conventional and plasmacytoid dendritic cells, respectively, and the frequencies of systemic natural killer cells. Our findings demonstrated that Cipro use altered immune responses of DM-colonized neonatal Gn pigs, while EcN supplementation rescued these immune parameters partially or completely.IMPORTANCE Rotavirus (RV) is a primary cause of malabsorptive diarrhea in children and is associated with significant morbidity and mortality, especially in developing countries. The use of antibiotics exacerbates intestinal microbial imbalance and results in the persistence of RV-induced diarrhea. Probiotics are now being used to treat enteric infections and ulcerative colitis. We showed previously that probiotics partially protected gnotobiotic (Gn) piglets against human RV (HRV) infection and decreased the severity of diarrhea by modulating immune responses. However, the interactions between antibiotic and probiotic treatments and HRV infection in the context of an established gut microbiota are poorly understood. In this study, we developed a Gn pig model to study antibiotic-probiotic-HRV interactions in the context of a defined commensal microbiota (DM) that mimics aspects of the infant gut microbiota. Our results provide valuable information that will contribute to the treatment of antibiotic- and/or HRV-induced diarrhea and may be applicable to other enteric infections in children.


Assuntos
Imunidade Adaptativa , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Escherichia coli/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata , Probióticos/administração & dosagem , Infecções por Rotavirus/prevenção & controle , Fatores Etários , Animais , Citocinas/imunologia , Modelos Animais de Doenças , Escherichia coli/classificação , Humanos , Rotavirus/imunologia , Infecções por Rotavirus/imunologia , Suínos
5.
Vet Res ; 50(1): 101, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783923

RESUMO

Vitamin A (VA) has pleiotropic effects on the immune system and is critical for mucosal immune function and intestinal lymphocyte trafficking. We hypothesized that oral VA supplementation of porcine epidemic diarrhea virus (PEDV)-infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV challenge. Gilts received daily oral retinyl acetate (30 000 IU) starting at gestation day 76 throughout lactation. At 3-4 weeks pre-partum, VA-supplemented (PEDV + VA) and non-supplemented (PEDV) gilts were PEDV or mock inoculated (mock + VA and mock, respectively). PEDV + VA gilts had decreased mean PEDV RNA shedding titers and diarrhea scores. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3-5 days post-partum. The survival rate of PEDV + VA litters was 74.2% compared with 55.9% in PEDV litters. Mock and mock + VA litter survival rates were 5.7% and 8.3%, respectively. PEDV + VA gilts had increased PEDV IgA antibody secreting cells and PEDV IgA antibodies in serum pre-partum and IgA+ß7+ (gut homing) cells in milk post piglet challenge compared with PEDV gilts. Our findings suggest that oral VA supplementation may act as an adjuvant during pregnancy, enhancing maternal IgA and lactogenic immune protection in nursing piglets.


Assuntos
Imunidade Materno-Adquirida/imunologia , Imunoglobulina A/imunologia , Sus scrofa/imunologia , Vitamina A/metabolismo , Vitaminas/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Vírus da Diarreia Epidêmica Suína/imunologia , Distribuição Aleatória , Vitamina A/administração & dosagem , Vitaminas/administração & dosagem
6.
J Antibiot (Tokyo) ; 70(4): 443-447, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27756911

RESUMO

Caliciviruses are contagious pathogens of humans and various animals. They are the most common cause of viral gastroenteritis in humans, and can cause lethal diseases in domestic animals such as cats, rabbits and immunocompromised mice. In this study, we conducted cytopathic effect-based screening of 2080 selected compounds from our in-house library to find antiviral compounds against three culturable caliciviruses: feline calicivirus, murine norovirus (MNV) and porcine sapovirus (PoSaV). We identified active six compounds, of which two compounds, both related to theaflavins, showed broad antiviral activities against all three caliciviruses; three compounds (abamectin, a mixture of avermectin B1a and B1b; avermectin B1a; and (-)-epigallocatechin gallate hydrate) were effective against PoSaV only; and a heterocyclic carboxamide derivative (BFTC) specifically inhibited MNV infectivity in cell cultures. Further studies of the antiviral mechanism and structure-activity relationship of theaflavins suggested the following: (1) theaflavins worked before the viral entry step; (2) the effect of theaflavins was time- and concentration-dependent; and (3) the hydroxyl groups of the benzocycloheptenone ring were probably important for the anti-calicivirus activity of theaflavins. Theaflavins could be used for the calicivirus research, and as potential disinfectants and antiviral reagents to prevent and control calicivirus infections in animals and humans.


Assuntos
Antivirais/farmacologia , Biflavonoides/farmacologia , Caliciviridae/efeitos dos fármacos , Catequina/farmacologia , Flavinas/farmacologia , Animais , Infecções por Caliciviridae , Calicivirus Felino/efeitos dos fármacos , Catequina/análogos & derivados , Gatos , Efeito Citopatogênico Viral/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Camundongos , Norovirus/efeitos dos fármacos , Estrutura Quaternária de Proteína , Sapovirus/efeitos dos fármacos , Relação Estrutura-Atividade
7.
Vaccine ; 32(7): 816-24, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24380684

RESUMO

Vitamin A deficiency (VAD) is associated with increased childhood mortality and morbidity in impoverished Asian and African countries, but the impact of VAD on rotavirus (RV) vaccine or infection is poorly understood. We assessed effects of gestational and dietary induced pre- and post-natal VAD and vitamin A supplementation on immune responses to a pentavalent rotavirus vaccine, RotaTeq(®) in a neonatal gnotobiotic pig model. Vaccine efficacy was assessed against virulent G1P[8] human rotavirus (HRV) challenge. VAD and vitamin A sufficient (VAS) piglets were derived from dietary VAD and VAS sows, respectively. VAD piglets had significantly lower levels of hepatic vitamin A compared to that of VAS piglets. RotaTeq(®)-vaccinated VAD piglets had 350-fold higher fecal virus shedding titers compared to vaccinated VAS piglets post-challenge. Only 25% of vaccinated non-vitamin A supplemented VAD piglets were protected against diarrhea compared with 100% protection rate in vaccinated non-supplemented VAS piglets post-challenge. Intestinal HRV specific immune responses were compromised in VAD piglets. Vaccinated VAD piglets had significantly lower ileal HRV IgG antibody secreting cell (ASC) responses (pre-challenge) and duodenal HRV IgA ASC responses (post-challenge) compared to vaccinated VAS piglets. Also, intestinal HRV IgA antibody titers were 11-fold lower in vaccinated VAD compared to vaccinated VAS piglets post-challenge. Persistently elevated levels of IL-8, a pro-inflammatory mediator, and lower IL-10 responses (anti-inflammatory) in vaccinated VAD compared to VAS piglets suggest more severe inflammatory responses in VAD piglets post-challenge. Moreover higher IFN-γ responses pre-challenge were observed in VAD compared to VAS piglets. The impaired vaccine-specific intestinal antibody responses and decreased immunoregulatory cytokine responses coincided with reduced protective efficacy of the RV vaccine against virulent HRV challenge in VAD piglets. In conclusion, VAD impaired antibody responses to RotaTeq(®) and vaccine efficacy. Oral supplementation of 100,000 IU vitamin A concurrent with RV vaccine failed to increase the vaccine efficacy in VAD piglets.


Assuntos
Imunidade Adaptativa , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Deficiência de Vitamina A/complicações , Animais , Animais Recém-Nascidos/imunologia , Anticorpos Antivirais/imunologia , Diarreia/prevenção & controle , Diarreia/virologia , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Vida Livre de Germes , Imunoglobulina A/imunologia , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-8/imunologia , Intestinos/imunologia , Infecções por Rotavirus/imunologia , Suínos , Vacinas Atenuadas/imunologia , Vitamina A/administração & dosagem , Deficiência de Vitamina A/imunologia
8.
PLoS One ; 8(12): e82966, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24312675

RESUMO

Rotaviruses (RV) are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD) gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV) vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS) sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα) cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12) and 2-3 fold lower anti-inflammatory (IL10) cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented) pigs had significantly higher serum IL12 (PID2) and IFNγ (PID6) compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more severe rotavirus infection and lower HRV vaccine efficacy.


Assuntos
Linfócitos B/imunologia , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Linfócitos T/imunologia , Deficiência de Vitamina A/imunologia , Deficiência de Vitamina A/fisiopatologia , Animais , Linfócitos T CD8-Positivos/metabolismo , Humanos , Interferon-alfa/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Rotavirus/patogenicidade , Suínos , Deficiência de Vitamina A/metabolismo
9.
Am J Vet Res ; 74(10): 1353-62, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24066921

RESUMO

OBJECTIVE: To investigate effects of low dietary vitamin A content on antibody responses in feedlot calves inoculated with an inactivated bovine coronavirus (BCoV) vaccine. ANIMALS: 40 feedlot calves. PROCEDURES: Calves were fed diets containing high (3,300 U/kg) or low (1,100 U/kg) amounts of vitamin A beginning on the day of arrival at a feedlot (day 0) and continuing daily until the end of the study (day 140). Serum retinol concentrations were evaluated in blood samples obtained throughout the study. Calves were inoculated IM with an inactivated BCoV vaccine on days 112 and 126. Blood samples obtained on days 112 and 140 were used for assessment of BCoV-specific serum IgG1, IgG2, IgM, and IgA titers via an ELISA. RESULTS: The low vitamin A diet reduced serum retinol concentrations between days 112 and 140. After the BCoV inoculation and booster injections, predominantly serum IgG1 antibodies were induced in calves fed the high vitamin A diet; however, IgG1 titers were compromised at day 140 in calves fed the low vitamin A diet. Other isotype antibodies specific for BCoV were not affected by the low vitamin A diet. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary vitamin A restriction increases marbling in feedlot cattle; however, its effect on antibody responses to vaccines is unknown. A low vitamin A diet compromised the serum IgG1 responses against inactivated BCoV vaccine, which suggested suppressed T-helper 2-associated antibody (IgG1) responses. Thus, low vitamin A diets may compromise the effectiveness of viral vaccines and render calves more susceptible to infectious disease.


Assuntos
Anticorpos Antivirais/efeitos dos fármacos , Bovinos/imunologia , Coronavirus Bovino/imunologia , Suplementos Nutricionais , Vacinas de Produtos Inativados/imunologia , Vitamina A/farmacologia , Animais , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática/veterinária , Imunoglobulina G/sangue , Injeções Intramusculares/veterinária , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Vacinas de Produtos Inativados/administração & dosagem , Vitamina A/sangue
10.
Vaccine ; 31(15): 1916-23, 2013 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-23453730

RESUMO

Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways.


Assuntos
Animais Recém-Nascidos/imunologia , Colostro/imunologia , Imunidade Humoral/imunologia , Leite Humano/imunologia , Probióticos/farmacologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Administração Oral , Animais , Animais Recém-Nascidos/microbiologia , Linfócitos B/imunologia , Bifidobacterium/imunologia , Bifidobacterium/fisiologia , Contagem de Colônia Microbiana , Colostro/química , Fezes/microbiologia , Feminino , Vida Livre de Germes , Humanos , Imunoglobulina A/análise , Imunoglobulina A/imunologia , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Lacticaseibacillus rhamnosus/imunologia , Lacticaseibacillus rhamnosus/fisiologia , Leite Humano/química , Modelos Animais , Probióticos/administração & dosagem , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Sus scrofa/imunologia , Sus scrofa/microbiologia , Fator de Crescimento Transformador beta/sangue , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
11.
J Immunol ; 190(9): 4742-53, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23536630

RESUMO

We examined how prenatally acquired vitamin A deficiency (VAD) modulates innate immune responses and human rotavirus (HRV) vaccine efficacy in a gnotobiotic (Gn) piglet model of HRV diarrhea. The VAD and vitamin A-sufficient (VAS) Gn pigs were vaccinated with attenuated HRV (AttHRV) with or without concurrent oral vitamin A supplementation (100,000 IU) and challenged with virulent HRV (VirHRV). Regardless of vaccination status, the numbers of conventional and plasmacytoid dendritic cells (cDCs and pDCs) were higher in VAD piglets prechallenge, but decreased substantially postchallenge as compared with VAS pigs. We observed significantly higher frequency of CD103 (integrin αEß7) expressing DCs in VAS versus VAD piglets postchallenge, indicating that VAD may interfere with homing (including intestinal) phenotype acquisition. Post-VirHRV challenge, we observed longer and more pronounced diarrhea and higher VirHRV fecal titers in nonvaccinated VAD piglets. Consistent with higher VirHRV shedding titers, higher IFN-α levels were induced in control VAD versus VAS piglet sera at postchallenge day 2. Ex vivo HRV-stimulated mononuclear cells (MNCs) isolated from spleen and blood of VAD pigs prechallenge also produced more IFN-α. In contrast, at postchallenge day 10, we observed reduced IFN-α levels in VAD pigs that coincided with decreased TLR3(+) MNC frequencies. Numbers of necrotic MNCs were higher in VAD pigs in spleen (coincident with splenomegaly in other VAD animals) prechallenge and intestinal tissues (coincident with higher VirHRV induced intestinal damage) postchallenge. Thus, prenatal VAD caused an imbalance in innate immune responses and exacerbated VirHRV infection, whereas vitamin A supplementation failed to compensate for these VAD effects.


Assuntos
Vida Livre de Germes/imunologia , Imunidade Inata/imunologia , Infecções por Rotavirus/imunologia , Rotavirus/imunologia , Deficiência de Vitamina A/congênito , Deficiência de Vitamina A/imunologia , Animais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Apoptose/imunologia , Diarreia/imunologia , Diarreia/metabolismo , Diarreia/virologia , Modelos Animais de Doenças , Feminino , Humanos , Cadeias alfa de Integrinas/imunologia , Cadeias alfa de Integrinas/metabolismo , Interferon gama/imunologia , Interferon gama/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/imunologia , Intestinos/virologia , Fígado/imunologia , Fígado/metabolismo , Fígado/virologia , Gravidez , Receptores do Ácido Retinoico/imunologia , Receptores do Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Proteínas Plasmáticas de Ligação ao Retinol/imunologia , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Infecções por Rotavirus/metabolismo , Infecções por Rotavirus/virologia , Baço/imunologia , Baço/metabolismo , Baço/virologia , Suínos , Deficiência de Vitamina A/metabolismo
12.
Vet Immunol Immunopathol ; 117(3-4): 236-48, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17403542

RESUMO

Maternal cytokines may play instructive roles in development of the neonatal immune system. However, cytokines in colostrum and milk and their transfer from mothers to neonates have not been well documented, except for TGF-beta. Swine provide a unique model to study lactogenic cytokines because the sow's impermeable placenta prohibits transplacental passage. We investigated IL-6 and TNF-alpha (pro-inflammatory), IFN-gamma and IL-12 (Th1), IL-10 and IL-4 (Th2) and TGF-beta1 (Th3) concentrations in sow serum and colostrum/milk and serum of their suckling and weaned piglets and in age-matched colostrum-deprived gnotobiotic piglets. All cytokines were detected in colostrum/milk and correlated with concentrations in sow serum except for mammary-derived TNF-alpha and TGF-beta1. Detection of IL-12 and TGF-beta1 in pre-suckling and colostrum-deprived gnotobiotic piglet serum suggests constitutive production: other cytokines were undetectable confirming absence of transplacental transfer. Peak median cytokine concentrations in suckling piglet serum occurred at post-partum days 1-2 (IL-4>IL-6>IFN-gamma>IL-10). The effects in vitro of physiologically relevant concentrations of the two predominant lactogenic cytokines (TGF-beta1 and IL-4) on porcine naive B cell responses to lipopolysaccharide (LPS) and rotavirus (RV) were investigated. High (10 ng/ml) TGF-beta1 suppressed immunoglobulin secreting cell responses to LPS and rotavirus; low concentrations (0.1 ng/ml) promoted isotype switching to IgA antibody. Interleukin-4 induced inverse dose-dependent (0.1 ng>10 ng/ml) isotype switching to IgA and enhanced IgM secreting cell responses to LPS and rotavirus. In summary, we documented the transfer and persistence of maternal cytokines from colostrum/milk to neonates and their potential role in Th-2 biased IgA responses and reduced immunologic responsiveness of neonates.


Assuntos
Animais Lactentes/imunologia , Colostro/imunologia , Citocinas/imunologia , Imunidade Materno-Adquirida , Sus scrofa/imunologia , Animais , Animais Recém-Nascidos/imunologia , Citocinas/análise , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Vida Livre de Germes , Gravidez , Sus scrofa/sangue
13.
Am J Vet Res ; 64(4): 485-90, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12693541

RESUMO

OBJECTIVE: To determine the prevalence, fecal shedding pattern, and association of bovine torovirus (BoTV) with diarrhea in veal calves at time of arrival and periodically throughout the first 35 days after their arrival on a veal farm. ANIMALS: 62 veal calves. PROCEDURE: Fecal samples collected on days 0, 4, 14, and 35 after arrival were tested for BoTV by use of ELISA and reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Paired serum samples obtained from blood collected on days 0 and 35 were analyzed for BoTV antibodies with a hemagglutination inhibition assay. Fecal samples were also screened for other enteric pathogens, including rotavirus, coronavirus, and Cryptosporidium spp. RESULTS: Fecal shedding of BoTV was detected in 15 of 62 (24%) calves by use of ELISA and RT-PCR assay, with peak shedding on day 4. A significant independent association between BoTV shedding and diarrhea was observed. In addition, calves shedding > or = 2 enteric pathogens were more likely to have diarrhea than calves shedding < or = 1 pathogen. Calves that were seronegative or had low antibody titers against BoTV (< or = 1:10 hemagglutination inhibition units) at arrival seroconverted to BoTV (> 4-fold increase in titer); these calves were more likely to shed virus than calves that were seropositive against BoTV at arrival. CONCLUSIONS AND CLINICAL RELEVANCE: Shedding of BoTV was strongly associated with diarrhea in neonatal veal calves during the first week after arrival at the farm. These data provide evidence that BoTV is an important pathogen of neonatal veal calves.


Assuntos
Doenças dos Bovinos/virologia , Diarreia/veterinária , Diarreia/virologia , Infecções por Torovirus/veterinária , Torovirus/isolamento & purificação , Torovirus/fisiologia , Eliminação de Partículas Virais , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Bovinos , Doenças dos Bovinos/diagnóstico , Colostro/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Coronavirus Bovino/isolamento & purificação , Diarreia/complicações , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Imunoglobulina G/análise , Masculino , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/isolamento & purificação , Infecções por Rotavirus/complicações , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/veterinária , Infecções por Rotavirus/virologia , Torovirus/genética , Torovirus/imunologia , Infecções por Torovirus/complicações , Infecções por Torovirus/diagnóstico , Infecções por Torovirus/virologia , Cultura de Vírus
14.
Adelantos microbiol. enfermedades infecc ; 7: 85-107, nov. 1988. tab
Artigo em Espanhol | LILACS | ID: lil-71991

RESUMO

Enteric viral infections in calves are widespread and most occur as enzootics in calves under 3 weeks of agne. Both clinical and subclinical infections occur, with the severity of the disease influenced by such factors as the level of passive immunity and the challenge dose and strain of virus. Rotaviruses and coronaviruses are primary enteric viral pathogens commonly associated with the neonatal calf diarrhea syndrome. Rotaviruses and coronaviruses replicate in intestinal villous enterocytes, resulting in villous atrophy and consequently a malabsorptive diarrhea. Two vaccination approaches have been developd to try to prevent rotavirus and coronavirus infections in calves. The first involves administrtion of modified live rotavirus and coronavirus to newborn calves to stimulate active immunity. This procedure was not efficacious under field conditions, presumably due to the widespread presence of maternal antibodies which neutralize the vaccine viruses. The second approach relies on rotavirus and coronavirus vaccination of cows to enhance antibody titers in mammary secretion and thus provide passive immunity. The variables involved in this latter approach using bovine rotavirus as a model are defined in this report. An analyses of passive and active immunity in calves supllemented with colostrum from rotavirus vaccinated cows and challenged by rotavirus is also desribed. Results indicate that a commercial vaccine failed to increase rotavirus antibody titers in mammary secretions, but experimental vaccines developed in this laboratory significantly increased such titers. Furthermore, passive protection against rotavirus was mediated by optimal levels of colostral rotavirus antibodies, primarily of the IgGl class, present at frequent intervals within the calfs intestine (lactogenic immunity). Serum antibodies alone in the newborn calf were less protective, but may moderate the severity of rotavirus infecctions


Assuntos
Bovinos , Animais , Feminino , Doença das Mucosas por Vírus da Diarreia Viral Bovina/imunologia , Imunidade Materno-Adquirida , Rotavirus/imunologia , Bovinos , Colostro/imunologia
15.
Adelantos microbiol. enfermedades infecc ; 7: 85-107, nov. 1988. Tab
Artigo em Espanhol | BINACIS | ID: bin-29012

RESUMO

Enteric viral infections in calves are widespread and most occur as enzootics in calves under 3 weeks of agne. Both clinical and subclinical infections occur, with the severity of the disease influenced by such factors as the level of passive immunity and the challenge dose and strain of virus. Rotaviruses and coronaviruses are primary enteric viral pathogens commonly associated with the neonatal calf diarrhea syndrome. Rotaviruses and coronaviruses replicate in intestinal villous enterocytes, resulting in villous atrophy and consequently a malabsorptive diarrhea. Two vaccination approaches have been developd to try to prevent rotavirus and coronavirus infections in calves. The first involves administrtion of modified live rotavirus and coronavirus to newborn calves to stimulate active immunity. This procedure was not efficacious under field conditions, presumably due to the widespread presence of maternal antibodies which neutralize the vaccine viruses. The second approach relies on rotavirus and coronavirus vaccination of cows to enhance antibody titers in mammary secretion and thus provide passive immunity. The variables involved in this latter approach using bovine rotavirus as a model are defined in this report. An analyses of passive and active immunity in calves supllemented with colostrum from rotavirus vaccinated cows and challenged by rotavirus is also desribed. Results indicate that a commercial vaccine failed to increase rotavirus antibody titers in mammary secretions, but experimental vaccines developed in this laboratory significantly increased such titers. Furthermore, passive protection against rotavirus was mediated by optimal levels of colostral rotavirus antibodies, primarily of the IgGl class, present at frequent intervals within the calfs intestine (lactogenic immunity). Serum antibodies alone in the newborn calf were less protective, but may moderate the severity of rotavirus infecctions (AU)


Assuntos
Bovinos , Animais , Feminino , Imunidade Materno-Adquirida , Rotavirus/imunologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/imunologia , Bovinos , Colostro/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA