50 research outputs found

    Chagasic Thymic Atrophy Does Not Affect Negative Selection but Results in the Export of Activated CD4+CD8+ T Cells in Severe Forms of Human Disease

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    Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery. To date, the effect of the changes promoted by the parasite infection on thymic central tolerance has remained elusive. Herein we show that the intrathymic key elements that are necessary to promote the negative selection of thymocytes undergoing maturation during the thymopoiesis remains functional during the acute chagasic thymic atrophy. Intrathymic expression of the autoimmune regulator factor (Aire) and tissue-restricted antigen (TRA) genes is normal. In addition, the expression of the proapoptotic Bim protein in thymocytes was not changed, revealing that the parasite infection-induced thymus atrophy has no effect on these marker genes necessary to promote clonal deletion of T cells. In a chicken egg ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic system, the administration of OVA peptide into infected mice with thymic atrophy promoted OVA-specific thymocyte apoptosis, further indicating normal negative selection process during the infection. Yet, although the intrathymic checkpoints necessary for thymic negative selection are present in the acute phase of Chagas disease, we found that the DP cells released into the periphery acquire an activated phenotype similar to what is described for activated effector or memory single-positive T cells. Most interestingly, we also demonstrate that increased percentages of peripheral blood subset of DP cells exhibiting an activated HLA-DR+ phenotype are associated with severe cardiac forms of human chronic Chagas disease. These cells may contribute to the immunopathological events seen in the Chagas disease

    Three-way interaction among plants, bacteria, and coleopteran insects

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    Comparative gut transcriptome analysis reveals differences between virulent and avirulent Russian wheat aphids, Diuraphis noxia

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    Citation: Anathakrishnan, R., Sinha, D. K., Murugan, M., Zhu, K. Y., Chen, M. S., Zhu, Y. C., & Smith, C. M. (2014). Comparative gut transcriptome analysis reveals differences between virulent and avirulent Russian wheat aphids, Diuraphis noxia. Retrieved from http://krex.ksu.eduThe Russian wheat aphid, Diuraphis noxia, is a destructive pest of cereal crops that exhibits virulence to D. noxia resistance genes in wheat. Therefore, it is important to identify D. noxia virulence factors. The insect gut, the primary site of defense to ingested toxins, is also a likely site of differential gene expression in virulent insects. Comparative analyses of gut transcriptomes from virulent and avirulent D. noxia can improve an understanding of aphid gut physiology and may reveal factors critical to compatible D. noxia-wheat interactions. A total of 4, 600 clones were sequenced from gut cDNA libraries prepared from avirulent (biotype 1) and virulent (biotype 2) D. noxia feeding on biotype 1-resistant wheat. A majority of the sequences (66% in biotype 1, 64% in biotype 2) matched those from the NR database. BLASTX analysis of sequences with the highest E-values revealed that 59% of the biotype 1 sequences matched those of the pea aphid, Acyrthosiphon pisum. However, only 17% of the biotype 2 sequences were similar to those of A. pisum. RT-qPCR expression analyses confirmed that the biotype 2 gut transcriptome differs significantly from that of biotype 1. A transcript coding the tRNA-Leu gene was significantly up-regulated in the biotype 2 transcriptome, strongly suggesting that leucine metabolism is a critical factor in biotype 2 survival. Many more transcripts encoding protease inhibitors occurred in the avirulent biotype 1 gut than in the gut of virulent biotype 2. However, more protease transcripts occurred in the biotype 2 gut than in the biotype 1 gut, suggesting that the avirulent biotype produces protease inhibitors in response to plant proteases. The virulent biotype 2 produces trypsin-like and chymotrypsin-like serine protease counter-defenses to overcome biotype 1-resistant plants

    Environment, interactions between Trypanosoma cruzi and its host, and health Meio-ambiente, interaçÔes entre Trypanosoma cruzi e seu hospedeiro e saĂșde humana

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    An epidemiological chain involving Trypanosoma cruzi is discussed at the environmental level, and in terms of fine molecular interactions in invertebrate and vertebrate hosts dwelling in different ecosystems. This protozoan has a complex, genetically controlled plasticity, which confers adaptation to approximately 40 blood-sucking triatomine species and to over 1,000 mammalian species, fulfilling diverse metabolic requirements in its complex life-cycle. The Tr. cruzi infections are deeply embedded in countless ecotypes, where they are difficult to defeat using the control methods that are currently available. Many more field and laboratory studies are required to obtain data and information that may be used for the control and prevention of Tr. cruzi infections and their various disease manifestations. Emphasis should be placed on those sensitive interactions at cellular and environmental levels that could become selected targets for disease prevention. In the short term, new technologies for social mobilization should be used by people and organizations working for justice and equality through health information and promotion. A mass media directed program could deliver education, information and communication to protect the inhabitants at risk of contracting Tr. cruzi infections.<br>Uma rede epidemiolĂłgica envolvendo o Trypanosoma cruzi foi discutida nos nĂ­veis ambientais e de interaçÔes moleculares nos hospedeiros que habitam em 19 diferentes ecossistemas. O protozoĂĄrio tem uma enorme plasticidade controlada geneticamente que confere sua adaptação a cerca de quarenta espĂ©cies de triatomĂ­neos e mais de mil espĂ©cies de mamĂ­feros. Essas infecçÔes estĂŁo profundamente embutidas em inĂșmeros ecĂłtopos, onde elas estĂŁo inacessĂ­veis aos mĂ©todos de controle utilizados. Muito mais estudos de campo e de laboratĂłrio sĂŁo necessĂĄrios Ă  obtenção de dados e informação pertinentes ao controle e prevenção das infecçÔes pelo Tr. cruzi e as vĂĄrias manifestaçÔes da doença. Ênfase deve ser dada Ă quelas interaçÔes que ocorrem nos nĂ­veis celulares e ambientais que se poderiam tomar como alvos seletivos para prevenção da doença. Novas tecnologias para mobilização social devem ser disponibilizadas para os que trabalham pela justiça e pela igualdade, mediante informação para a promoção da saĂșde. Um programa direcionado de educação de massa pode prover informação e comunicação necessĂĄrias para proteger os habitantes atualmente expostos ao risco de contrair as infecçÔes pelo Tr. cruzi
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