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1.
Clin Exp Immunol ; 196(3): 364-373, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30724349

RESUMO

Infections with Schistosoma mansoni remain a major health problem in the Sudan where endemic communities, such as those in Kassala and Khartoum states, continue to face severe social-economic difficulties. Our previous immunoepidemiological findings revealed different immune [cytokine and S. mansoni egg (SEA) antibody] profiles in individuals with active infections (eggs in stool n = 110), individuals positive for S. mansoni via polymerase chain reaction (PCR) using sera (SmPCR+ n = 63) and those uninfected (Sm uninf). As antibody responses to eggs and worms are known to change during infection, we have expanded the profiling further by determining levels of adult worm (SWA) antibodies and nine chemokines in the serum of each individual in the three different cohorts. With the exception of C-C motif chemokine ligand (CCL)2, all measured chemokines were significantly higher in SmPCR+ individuals when compared to the egg+ group and in addition they also presented elevated levels of SWA-specific immunoglobulin (Ig)G2. Multivariable regression analysis further revealed that infection per se was strongly linked to SWA-specific IgG3 levels and CCL5 was strongly associated with a SmPCR+ diagnostic state. In the absence of PCR diagnostics that recognize juvenile worms or schistosomulae motives, identifying schistosome-specific traits should provide better insights into current prevalence rates in endemic communities and, in doing so, take into consideration PCR+ non-egg+ individuals in current treatment programmes.


Assuntos
Quimiocinas/sangue , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Estudos de Coortes , Ovos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Esquistossomose mansoni/diagnóstico , Sudão , Regulação para Cima , Adulto Jovem
2.
Parasite Immunol ; 37(2): 97-104, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25559085

RESUMO

Schistosome infections are renowned for their ability to induce regulatory networks such as regulatory T cells (Treg) that control immune responses against homologous and heterologous antigens such as allergies. However, in the case of co-infections with hepatitis C virus (HCV), schistosomes accentuate disease progression and we hypothesized that expanding schistosome-induced Treg populations change their phenotype and could thereby suppress beneficial anti-HCV responses. We therefore analysed effector T cells and n/iTreg subsets applying the markers Granzyme B (GrzB) and Helios in Egyptian cohorts of HCV mono-infected (HCV), schistosome-co-infected (Sm/HCV) and infection-free individuals. Interestingly, viral load and liver transaminases were significantly elevated in Sm/HCV individuals when compared to HCV patients. Moreover, overall Treg frequencies and Helios(pos) Treg were not elevated in Sm/HCV individuals, but frequencies of GrzB(+) Treg were significantly increased. Simultaneously, GrzB(+) CD8(+) T cells were not suppressed in co-infected individuals. This study demonstrates that in Sm/HCV co-infected cohorts, liver disease is aggravated with enhanced virus replication and Treg do not expand but rather change their phenotype with GrzB possibly being a more reliable marker than Helios for iTreg. Therefore, curing concurrent schistosome disease could be an important prerequisite for successful HCV treatment as co-infected individuals respond poorly to interferon therapy.


Assuntos
Coinfecção/imunologia , Hepacivirus/fisiologia , Hepatite C Crônica/imunologia , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Animais , Feminino , Humanos , Interleucina-8/imunologia , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Carga Viral
3.
Clin Exp Immunol ; 178(2): 212-23, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24943899

RESUMO

Overall asthmatic symptoms can be controlled with diverse therapeutic agents. However, certain symptomatic individuals remain at risk for serious morbidity and mortality, which prompts the identification of novel therapeutic targets and treatment strategies. Thus, using an adjuvant-free T helper type 2 (Th2) murine model, we have deciphered the role of interleukin (IL)-1 signalling during allergic airway inflammation (AAI). Because functional IL-1ß depends on inflammasome activation we first studied asthmatic manifestations in specific inflammasome-deficient [NACHT, LRR and PYD domains-containing protein 3 (NLRP3(-/-) ) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC(-/-) )] and IL-1 receptor type 1(-/-) (IL-1R1(-/-) ) mice on the BALB/c background. To verify the onset of disease we assessed cellular infiltration in the bronchial regions, lung pathology, airway hyperresponsiveness and ovalbumin (OVA)-specific immune responses. In the absence of NLRP3 inflammasome-mediated IL-1ß release all symptoms of AAI were reduced, except OVA-specific immunoglobulin levels. To address whether manipulating IL-1 signalling reduced asthmatic development, we administered the IL-1R antagonist anakinra (Kineret®) during critical immunological time-points: sensitization or challenge. Amelioration of asthmatic symptoms was only observed when anakinra was administered during OVA challenge. Our findings indicate that blocking IL-1 signalling could be a potential complementary therapy for allergic airway inflammation.


Assuntos
Proteínas de Transporte/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Hipersensibilidade Respiratória/metabolismo , Doença Aguda , Animais , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinofilia/genética , Eosinofilia/imunologia , Feminino , Células Caliciformes/patologia , Hiperplasia , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ovalbumina/efeitos adversos , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Receptores Tipo I de Interleucina-1/deficiência , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
4.
Clin Exp Immunol ; 175(2): 246-57, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24168057

RESUMO

Fatalities from schistosome infections arise due to granulomatous, immune-mediated responses to eggs that become trapped in host tissues. Schistosome-specific immune responses are characterized by initial T helper type 1 (Th1) responses and our previous studies demonstrated that myeloid differentiation primary response gene 88 (Myd88)-deficient mice failed to initiate such responses in vivo. Paradoxically, schistosomal antigens fail to stimulate innate cells to release proinflammatory cytokines in vitro. Since Schistosoma mansoni infection is an intestinal disease, we hypothesized that commensal bacteria could act as bystander activators of the intestinal innate immune system to instigate Th1 responses. Using a broad spectrum of orally administered antibiotics and anti-mycotics we analysed schistosome-infected mice that were simultaneously depleted of gut bacteria. After depletion there was significantly less inflammation in the intestine, which was accompanied by decreased intestinal granuloma development. In contrast, liver pathology remained unaltered. In addition, schistosome-specific immune responses were skewed and faecal egg excretion was diminished. This study demonstrates that host microbiota can act as a third partner in instigating helminth-specific immune responses.


Assuntos
Granuloma/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Microbiota/imunologia , Schistosoma mansoni/imunologia , Esquistossomose/imunologia , Animais , Antibacterianos/administração & dosagem , Fezes/microbiologia , Fezes/parasitologia , Feminino , Granuloma/metabolismo , Interações Hospedeiro-Parasita/imunologia , Inflamação/imunologia , Inflamação/parasitologia , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Intestinos/patologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Carga Parasitária , Esquistossomose/microbiologia , Células Th1/imunologia
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