Extract of Ascaris suum induces TGF-ß and early production of IgG1 in experimental autoimmune hepatitis / Extrato de Ascaris suum induz TGF-ß e produção precoce de IgG1 na hepatite autoimune experimental

Abstract In experimental autoimmune hepatitis (EAH) of Th1 profile, an extract of adult Ascaris suum worms (ASC) was previously found to deviate the immune response to a Th2/IL-10 pattern. Here, the effects of treatment with ASC on production of TGF-β and the anti-Ascaris isotypes IgG1 and IgG2a in EAH were evaluated. EAH was induced in BALB/c mice, intravenously with concanavalin A. Two hours later, these animals received ASC (EAH+ASC group) or PBS vehicle (EAH group). IgG1 and IgG2a were evaluated 8 h, 24 h and 7 d after induction. TGF-β was measured in a splenocyte culture at this last time. The isotype levels in the EAH group were low throughout the kinetics. In the EAH+ASC group, there was significant production of IgG1 at 24 h and 7 d, but of IgG2a only at 7 d. There was statistically greater production of TGF-β in the EAH+ASC group. The higher levels of IgG1 and TGF-β in this group suggest that an additional Th1 response control route exists in EAH, which needs to be investigated.

Resumo Na hepatite autoimune experimental (HAE) de perfil Th1, o extrato de vermes adultos Ascaris suum (ASC) desviou a resposta imune para um padrão Th2/IL-10. Neste trabalho, foram avaliados os efeitos do tratamento com ASC na produção TGF-β e dos isótipos de IgG1 e IgG2a anti-Ascaris na HAE. Esta foi induzida em camundongos BALB/c intravenosamente com Concanavalina A. Após duas horas, os animais receberam ASC (grupo HAE+ASC) ou veículo PBS (grupo HAE). IgG1 e IgG2a foram avaliados em 8 horas, 24 horas e 7 dias após indução. TGF-β foi mensurado em cultura de esplenócitos nesse último tempo. Os níveis dos isótipos no grupo HAE foram baixos durante toda a cinética. No grupo HAE+ASC, houve produção significativa de IgG1 em 24 horas e 7 dias, mas somente em 7 dias para IgG2a. A produção de TGF-β foi estatisticamente maior no grupo HAE+ASC. Níveis mais altos de IgG1 e TGF-β nesse grupo sugerem uma via adicional de controle da resposta Th1 na HAE que precisa ser investigada.

Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring

BACKGROUND Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.

Maternal schistosomiasis: IL-2, IL-10 and regulatory T lymphocytes to unrelated antigen in adult offspring mice

Abstract INTRODUCTION: We evaluated IL-10, IL-2 and regulatory T cells (Treg), in response to ovalbumin (OA), in offspring from schistosomotic mouse mothers. METHODS: We used animals born (BIM) or suckled (SIM) from infected mothers; and mice born/suckled from infected (BSIM) or non-infected mothers (CONTROL). After OA+adjuvant immunization, spleen cells were cultured, with or without OA, and doubly marked for cytometry. RESULTS: BIM showed fewer CD4+/IL-2+ and more B220+/IL-10+ cells, whereas the SIM group showed increased Treg frequency. BSIM had fewer B220+/IL-10+ and Treg cells. CONCLUSIONS: Separately, gestation or nursing induced immunosuppressive cells in infected mothers, but improved anti-OA immunity when combined.

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Features to validate cerebral toxoplasmosis

Introduction Neurotoxoplasmosis (NT) sometimes manifests unusual characteristics. Methods We analyzed 85 patients with NT and AIDS according to clinical, cerebrospinal fluid, cranial magnetic resonance, and polymerase chain reaction (PCR) characteristics. Results In 8.5%, focal neurological deficits were absent and 16.4% had single cerebral lesions. Increased sensitivity of PCR for Toxoplasma gondii DNA in the central nervous system was associated with pleocytosis and presence of >4 encephalic lesions. Conclusions Patients with NT may present without focal neurological deficit and NT may occur with presence of a single cerebral lesion. Greater numbers of lesions and greater cellularity in cerebrospinal fluid improve the sensitivity of PCR to T gondii. .

Transferência passiva de anticorpos específicos para antígenos de Schistosoma mansoni em camundongos nascidos ou amamentados em mães esquistossomóticas / Passive transfer of Schistosoma mansoni antigens-specific antibodies in mice born or suckled by schistosomotic mothers

Objetivo - Estudos experimentais demonstraram que mães infectadas pelo Schistosoma mansoni modulam a imunidade para antígenos homólogos, dos descendentes adultos, através do contato prévio com anticorpos anti-Schistosoma durante o período pré-natal junto à amamentação. Descendentes adultos de mães esquistossomóticas apresentaram alteração na imunidade para um antígeno heterólogo, Ovalbumina (OA): amamentação induziu maior produção de imunoglobulinas anti-OA, enquanto a gestação levou à supressão destas imunoglobulinas. A fim de esclarecer a participação dos anticorpos anti-Schistosoma maternos na alteração da imunidade dos descendentes adultos, os anticorpos contra antígenos solúveis dos ovos (SEA) e dos vermes (SWAP) em descendentes gerados ou apenas amamentados em mães esquistossomóticas foram dosados. Métodos - Camundongos recém-nascidos foram divididos em: animais nascidos de Mães Infectadas (MI) e amamentados em mães não-infectadas; animais nascidos de mães não-infectadas e Amamentados em mães Infectadas (AI); animais nascidos e amamentados em mães infectadas (MIAI) ou não-infectadas (Controle). Os animais foram sangrados 21, 45, 60 e 77 dias, após nascimento e os isótipos IgG1 e IgG2a dosados, no plasma, por ELISA. Resultados - Foi detectado IgG1, mas não IgG2a, principalmente anti-SEA, tanto no grupo MI como nos grupos AI e MIAI. A transferência pela amamentação foi mais efetiva (maiores níveis e manutenção durante a cinética). Conclusões - O isótipo IgG1 anti-SEA presente no grupo MI, bem como no grupo AI, exclui a associação dos anticorpos antiparasita e melhora da imunidade heteróloga dos descendentes amamentados em mães esquistossomótica. Este estudo enfoca o importante papel da amamentação em transferir de forma eficaz anticorpos anti-SEA para indivíduos de área endêmica para esquistossomose.

Objective - Experimental studies have demonstrated that Schistosoma mansoni infected mothers modulate immunity to homologous antigen, in their adult offspring, through prior contact with anti-Schistosoma antibodies during the prenatal period plus breastfeeding. Adult offspring of schistosomotic mothers showed alterations in immunity to a heterologous antigen, ovalbumin (OA): breastfeeding induced higher production of anti-OA immunoglobulin, while the pregnancy led to suppression of this immunoglobulin. In order to study the participation of the maternal anti-Schistosoma antibodies and change in the heterologous immunity in adult offspring, antibodies against soluble egg antigen (SEA) and worms (SWAP) in offspring born or only breastfed by schistosomotic mothers were measured. Methods - Newborn mice were divided into: animals Born from Infected Mothers (BIM) suckled by non-infected mothers; animals from non-infected mothers Suckled by Infected Mothers (SIM); and mice Born and Suckled in Infected Mothers (BSIM) or non-infected (Control) mothers. The animals were bled 21,45, 60, 77 days, after birth, and IgG1 and IgG2a serum isotypes were measured by ELISA. Results - It was detected IgG1, but not IgG2a, mainly anti-SEA in a group BIM and in the groups SIM and BSIM. The transfer by breastfeeding was more effective (higher levels and maintenance during the kinetic). Conclusions - The anti-SEA IgG1 isotype detected in the group BIM, as well as, in the SIM, excludes the association of anti-parasite antibodies and the improvement of heterologous immunity in offspring nursed by schistosomotic mothers. This study highlights the important role of breastfeeding as effective way to transfer anti-SEA antibodies for individuals from an endemic area for schistosomiasis.