Mostrando recursos 1 - 20 de 40

  1. Early skin immunological disturbance after Plasmodium-infected mosquito bites

    Silva, Henrique Borges da; Caetano, Susana S; Monteiro, Isadora; Gómez-Conde, Iván; Hanson, Kirsten; Penha-Gonçalves, Carlos; Olivieri, David N; Mota, Maria M; Marinho, Cláudio R.; D’Imperio Lima, Maria R.; Tadokoro, Carlos E
    Although the role of regulatory T cells (Tregs) during malaria infection has been studied extensively, such studies have focused exclusively on the role of Treg during the blood stage of infection; little is known about the detailed mechanisms of Tregs and sporozoite deposition in the dermis by mosquito bites. In this paper we show that sporozoites introduced into the skin by mosquito bites increase the mobility of skin Tregs and dendritic cells (DCs). We also show differences in MHC class II and/or CD86 expression on skin-resident dendritic cell subtypes and macrophages. From the observed decrease of the number of APCs...

  2. The Liver Plays a Major Role in Clearance and Destruction of Blood Trypomastigotes in Trypanosoma cruzi Chronically Infected Mice

    Sardinha, L. R.; Mosca, T.; Elias, R. M.; do Nascimento, R. S.; Goncalves, L. A.; Bucci, D. Z.; Marinho, C. R. F.; Penha-Goncalves, C.; Lima, M. R. D.; Alvarez, J. M.
    Intravenous challenge with Trypanosoma cruzi can be used to investigate the process and consequences of blood parasite clearance in experimental Chagas disease. One hour after intravenous challenge of chronically infected mice with 5x10(6) trypomastigotes, the liver constituted a major site of parasite accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were visualized at this time point scattered in the liver parenchyma. Moreover, at this time, many of liver-cleared parasites were viable, as estimated by the frequency of positive cultures, which considerably diminished after 48 h. Following clearance, the number of infiltrating cells in the hepatic tissue notably increased:...

  3. Transforming Growth Factor Beta 2 and Heme Oxygenase 1 Genes Are Risk Factors for the Cerebral Malaria Syndrome in Angolan Children

    Sambo, Maria Rosário; Trovoada, Maria Jesus; Benchimol, Carla; Quinhentos, Vatúsia; Gonçalves, Lígia; Velosa, Rute; Marques, Maria Isabel; Sepúlveda, Nuno; Clark, Taane G.; Mustafa, Stefan; Wagner, Oswald; Coutinho, António; Penha-Gonçalves, Carlos; Rodrigues, Mauricio Martins
    BACKGROUND: Cerebral malaria (CM) represents a severe outcome of the Plasmodium falciparum infection. Recent genetic studies have correlated human genes with severe malaria susceptibility, but there is little data on genetic variants that increase the risk of developing specific malaria clinical complications. Nevertheless, susceptibility to experimental CM in the mouse has been linked to host genes including Transforming Growth Factor Beta 2 (TGFB2) and Heme oxygenase-1 (HMOX1). Here, we tested whether those genes were governing the risk of progressing to CM in patients with severe malaria syndromes. METHODOLOGY/PRINCIPAL FINDINGS: We report that the clinical outcome of P. falciparum infection in a cohort of...

  4. Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients

    Fourati, Hajer; Bouzid, Dorra; Abida, Olfa; Kharrat, Najla; Mnif, Fatma; Haddouk, Samy; Fesel, Constantin; Costa, João; Ayed, Mourad Ben; Abid, Mohamed; Rebai, Ahmed; Penha-Gonçalves, Carlos; Masmoudi, Hatem
    Autoimmune Polyglandular Syndrome Type II (APSII) is characterized by the co-occurrence of clinical insufficiency of at least two endocrine glands. Although, HLA determinants of APSII predisposition have been identified, little attention has been paid to non-HLA genes. Here, we used SNP genotyping in a Sequenom platform and genetic association tests to study a cohort of 60 APSII Tunisian patients presenting highly frequent co-occurrence of Autoimmune Thyroid Disease (AITD) and Type 1 Diabetes (T1D) and lower frequency of Addison's disease (AD). We tested the high a priori possibility that well-established non-HLA autoimmunity loci were involved in APSII and confirmed five association...

  5. Innate stimulation of B1a cells enhances the autoreactive IgM repertoire in the NOD mouse: implications for type 1 diabetes

    Côrte-Real, J; Duarte, N.; Tavares, L; Penha-Gonçalves, C

  6. Regulatory T cells Contribute to Diabetes Protection in Lipopolysaccharide-Treated Non-Obese Diabetic Mice

    Caramalho, I; Rodrigues-Duarte, L; Perez, A; Zelenay, S; Penha-Gonçalves, C; Demengeot, J.
    It is well established that viral, parasitic or bacterial infections can prevent type 1 diabetes (T1D) occurrence in non-obese diabetic (NOD) mice. On the other hand, defects in CD4(+) Regulatory T cell (Treg) numbers and/or function contribute to T1D aetiology in NOD mice and in humans. In this work, we formally tested whether the protective role of the bacterial product lipopolysaccharide (LPS) on diabetes incidence results from enhanced Treg activity. We first report that weekly administration of LPS to young prediabetic NOD mice, presenting or not insulitis at the time of treatment, afforded full protection from diabetes. Taking advantage from...

  7. Association of the RAVER2 gene with increased susceptibility for ulcerative colitis

    Bouzid, D.; Fourati, H.; Amouri, A.; Marques, I.; Abida, O.; Haddouk, S.; Ben Ayed, M.; Tahri, N.; Penha-Gonçalves, C; Masmoudi, H.
    Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE) and autoimmune polyglandular syndromes (APS) are autoimmune diseases (ADs) that may share common susceptibility pathways. We examined ribonucleo-protein, polypyrimidine tract-binding protein (PTB)-binding 2 (RAVER2) loci for these diseases in a cohort of 39 CD cases, 67 UC cases, 93 SLE cases, 60 APS cases and 162 healthy control subjects of Tunisian origin. We genotyped 3 SNPs of RAVER2 (rs2780814, rs1333739 and rs2780889) and evaluated it genetic association with each ADs, using X2-test. For each association, odds ratio (OR) and 95% CI were calculated. We show that rs2780814 is significantly associated...

  8. The {CREM} gene is involved in genetic predisposition to inflammatory bowel disease in the Tunisian population

    Bouzid, Dorra; Fourati, Hajer; Amouri, Ali; Marques, Isabel; Abida, Olfa; Haddouk, Samy; Ben Ayed, Mourad; Tahri, Nabil; Penha-Gonçalves, Carlos; Masmoudi, Hatem
    The identification of susceptibility genes for inflammatory bowel disease (IBD) is key to understanding pathogenic mechanisms. Recently, the results of genetic association studies have highlighted many loci that are shared among several autoimmune diseases. We aimed to study the genetic epidemiology of polymorphisms in specific genes previously associated with other autoimmune diseases, namely the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes. Twelve polymorphisms in the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes were genotyped in a cohort of 107 IBD patients (39 Crohn's disease [CD] and 68 ulcerative colitis [UC]) and 162 controls from southern Tunisia. One CREM single nucleotide...

  9. IFNAR1 Controls Progression to Cerebral Malaria in Children and CD8+ T Cell Brain Pathology in Plasmodium berghei-Infected Mice

    Ball, E. A.; Sambo, M. R.; Martins, M.; Trovoada, M. J.; Benchimol, C.; Costa, J.; Antunes Goncalves, L.; Coutinho, A.; Penha-Goncalves, C.
    Malaria in pregnancy is exquisitely aggressive, causing a range of adverse maternal and fetal outcomes prominently linked to Plasmodium-infected erythrocyte cytoadherence to fetal trophoblast. To elucidate the physiopathology of infected erythrocytes (IE) sequestration in the placenta we devised an experimental system for intravital placental examination of P. berghei-infected mice. BALB/c females were mated to C57Bl/6 CFP+ male mice and infected with GFP+ P. berghei IE, and at gestational day 18, placentas were exposed for time-lapse imaging acquisition under two-photon microscopy. Real-time images and quantitative measurements revealed that trophoblast conformational changes transiently restrain blood flow in the mouse placental labyrinth. The...

  10. A genome-wide survey of sRNAs in the symbiotic nitrogen-fixing alpha-proteobacterium Sinorhizobium meliloti

    Schluter, J.P.; Reinkensmeier, J.; Daschkey, S.; Evguenieva-Hackenberg, E.; Janssen, S.; Janicke, S.; Becker, J.D.; Giegerich, R.; Becker, A.
    A total of 1,125 sRNA candidates that were classified as trans-encoded sRNAs (173), cis-encoded antisense sRNAs (117), mRNA leader transcripts (379), and sense sRNAs overlapping coding regions (456) were identified in a size range of 50 to 348 nucleotides. Among these were transcripts corresponding to 82 previously reported sRNA candidates. Enrichment for RNAs with primary 5'-ends prior to sequencing of cDNAs suggested transcriptional start sites corresponding to 466 predicted sRNA regions. The consensus sigma70 promoter motif CTTGAC-N17-CTATAT was found upstream of 101 sRNA candidates. Expression patterns derived from microarray hybridizations provided further information on conditions of expression of a number...

  11. A genomewide survey of sRNAs in the symbiotic nitrogen-fixing alpha-proteobacterium Sinorhizobium meliloti

    Schluter, J.P.; Reinkensmeier, J.; Daschkey, S.; Evguenieva-hackenberg, E.; Janssen, S.; Janicke, S.; Becker, J.D.; Giegerich, R.; Becker, A.
    A total of 1,125 sRNA candidates that were classified as trans-encoded sRNAs (173), cis-encoded antisense sRNAs (117), mRNA leader transcripts (379), and sense sRNAs overlapping coding regions (456) were identified in a size range of 50 to 348 nucleotides. Among these were transcripts corresponding to 82 previously reported sRNA candidates. Enrichment for RNAs with primary 5'-ends prior to sequencing of cDNAs suggested transcriptional start sites corresponding to 466 predicted sRNA regions. The consensus sigma70 promoter motif CTTGAC-N17-CTATAT was found upstream of 101 sRNA candidates. Expression patterns derived from microarray hybridizations provided further information on conditions of expression of a number...

  12. Clusters of cytokines determine malaria severity in Plasmodium falciparum - Infected patients from endemic areas of central India

    Prakash, D.; Fesel, C.; Jain, R.; Cazenave, P.A.; Mishra, G.C.; Pied, S.
    We investigated the role of interferon (IFN)- gamma , interleukin (IL)-1 beta , IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)- alpha , and transforming growth factor (TGF)- beta in clinically well-defined groups of Plasmodium falciparum-infected patients manifesting mild malaria (MM), severe noncerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria-endemic site in India, as well as in healthy subjects from non-malaria-endemic areas. Two-way coupled cluster analysis revealed 2 clusters of cytokines relevant to clinical subgroups of disease. The first cluster was composed of IFN- gamma , IL-2, IL-5, IL-6, and IL-12,...

  13. Increased polyclonal immunoglobulin reactivity toward human and bacterial proteins is associated with clinical protection in human Plasmodium infection

    Fesel, C.; Goulart, L.F.; Neto, A.S.; Coelho, A.; Fontes, C.J.F.; Braga, E.M.; Vaz, N.M.
    The observed difference in polyclonal antibody production seems related to intrinsic activation states of infected individuals, rather than to parasite-antigen specific immune responses. However, it appears influenced by preceding stimuli. This supports the idea that acquired clinical immunity may not exclusively depend on antigen-specific responses, but also on the individual polyclonal reaction.

  14. Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status

    Duarte, J.; Deshpande, P.; Guiyedi, V.; Mecheri, S.; Fesel, C.; Cazenave, P.A.; Mishra, G.C.; Kombila, M.; Pied, S.
    Blood samples were collected from controls and P. falciparum-infected patients before treatment on the day of hospitalization (day 0) in India and, in addition, on days 7 and 30 after treatment in Gabon. Total IgE levels were determined by ELISA and functional P. falciparum-specific IgE were estimated using a mast cell line RBL-2H3 transfected with a human Fcε RI α-chain that triggers degranulation upon human IgE cross-linking. Mann Whitney and Kruskall Wallis tests were used to compare groups and the Spearman test was used for correlations. Total IgE levels were confirmed to increase upon infection and differ with level of transmission...

  15. Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children

    Guiyedi, V.; Chanseaud, Y.; Fesel, C.; Snounou, G.; Rousselle, J.C.; Lim, P.; Koko, J.; Namane, A.; Cazenave, P.A.; Kombila, M.; Pied, S.
    Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children

  16. IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India

    Bansal, D.; Herbert, F.; Lim, P.; Deshpande, P.; Becavin, C.; Guiyedi, V.; de Maria, I.; Rousselle, J.C.; Namane, A.; Jain, R.; Cazenave, P.A.; Mishra, G.C.; Ferlini, C.; Fesel, C.; Benecke, A.; Pied, S.
    We investigated the significance of these self-reactive antibodies in clinically well-defined groups of P. falciparum infected patients manifesting mild malaria (MM), severe non-cerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria epidemic site in central India using quantitative immunoprinting and multivariate statistical analyses. A two-fold complete-linkage hierarchical clustering allows classifying the different patient groups and to distinguish the CM from the others on the basis of their profile of IgG reactivity to brain proteins defined by PANAMA Blot. We identified beta tubulin III (TBB3) as a novel discriminant brain antigen in the prevalence of...

  17. Spatial Variation in Density and Total Size Estimates in Fragmented Primate Populations: The Golden-Crowned Sifaka (Propithecus tattersalli)

    Quemere, E.; Champeau, J.; Besolo, A.; Rasolondraibe, E.; Rabarivola, C.
    The golden-crowned sifaka (Propithecus tattersalli) is an endangered lemur species found only in the Daraina region, a very restricted area in north-eastern Madagascar. Its forest habitat is highly fragmented and expected to suffer from significant changes in the near future. The species is poorly known and only one census study, carried out in 2000, has ever been published. It is thus crucial to update the conservation status of the golden-crowned sifaka. before major anthropogenic environmental changes take place. Using the line-transect approach, we estimated the species density in the main forest fragments located in both the peripheral and central parts...

  18. The utility of existing passerine microsatellite markers for genetic studies in endangered species: as demonstrated for a critically endangered forest bird endemic to Réunion Island, the Réunion cuckooshrike (Coracina newtoni)

    Salmona, J.; Dawson, DA.; Fouillot, D.; Ghestemme, T.; Thebaud, C.; Chikhi, L.; Salamolard, M.
    Genetic data are increasingly recognized for their utility in conservation programs. However, many endangered species belong to families that have been understudied. Due to the urgency of their conservation status it is important to quickly identify polymorphic microsatellite loci from available resources. We show for the Re´union Cuckoo shrike Coracina newtoni, that this strategy can be very useful. Using 110 passerine microsatellite primer sets we identified eighteen polymorphic loci and tested them in 25 C. newtoni individuals. Following a Bonferroni correction one pair of loci displayed linkage disequilibrium

  19. Landscape genetics of an endangered lemur (Propithecus tattersalli) within its entire fragmented range

    Quemere, E.; Crouau-Roy, B.; Rabarivola, C.; Louis, EE.; Chikhi, L.
    Habitat fragmentation may strongly reduce individuals' dispersal among resource patches and hence influence population distribution and persistence. We studied the impact of landscape heterogeneity on the dispersal of the golden-crowned sifaka (Propithecus tattersalli), an endangered social lemur species living in a restricted and highly fragmented landscape. We combined spatial analysis and population genetics methods to describe population units and identify the environmental factors which best predict the rates and patterns of genetic differentiation within and between populations. We used non-invasive methods to genotype 230 individuals at 13 microsatellites in all the main forest fragments of its entire distribution area. Our...

  20. 2BAD: an application to estimate the parental contributions during two independent admixture events

    Bray, TC.; Sousa, VC.; Parreira, B.; Bruford, MW.; Chikhi, L.
    Several approaches have been developed to calculate the relative contributions of parental populations in single admixture event scenarios, including Bayesian methods. In many breeds and populations, it may be more realistic to consider multiple admixture events. However, no approach has been developed to date to estimate admixture in such cases. This report describes a program application, 2BAD (for 2-event Bayesian ADmixture), which allows the consideration of up to two independent admixture events involving two or three parental populations and a single admixed population, depending on the number of populations sampled. For each of these models, it is possible to estimate...

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