59 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
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