Effects of Plasmodium berghei on thymus: high levels of apoptosis and premature egress of CD4(+)CD8(+) thymocytes in experimentally infected mice |
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Authors: | Francelin Carolina Paulino Luciana Campos Gameiro Jacy Verinaud Liana |
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Affiliation: | a Department of Anatomy, Cell Biology and Physiology, Biology Institute, State University of Campinas - UNICAMP, Barão Geraldo, Campinas CEP: 13083-970, São Paulo, Brazil b Center of Natural and Human Sciences, Federal University of ABC-UFABC, São Paulo, Brazil c Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora - UFJF, Juiz de Fora, Minas Gerais, Brazil |
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Abstract: | We have previously showed alterations in the thymus during experimental infection with Plasmodium berghei, the causative agent of Malaria. Such alterations comprised histological changes with loss of delimitation between cortical and medullar regions, a profound atrophy with depletion of CD4+CD8+ double-positive (DP) thymocytes, and severe changes in the expression of cell migration-related molecules, belonging to the extracellular matrix and chemokine protein families. Taken together, these considerations prompted us to evaluate if the acute thymic atrophy observed during Plasmodium infection was correlated with increased apoptotic levels of thymocytes or with their premature emigration to the periphery. Our results confirmed that the marked reduction of the thymus weight in infected animals was accompanied by histological alterations, which included a very large number of cells showing nuclear condensation and karyorrhectic changes surrounded by histiocytes suggesting increased levels of apoptosis. This was confirmed by immunohistochemistry and flow cytometry techniques. In order to verify if an accelerated emigration of thymic cells to the peripheral lymphoid organs was also occurring we analyzed the spleen and mesenteric lymph nodes from control and infected mice. No significant differences were found in the spleen, but were seen after 14 days of infection between control and infected mice in the mesenteric lymph nodes. The main alteration was the presence of double negative (CD4−CD8−) and double positive (CD4+CD8+) cells. We concluded that both apoptosis of thymocytes and premature egress of immature cells take place during infection. Additional studies will be necessary to verify how such alterations might influence the systemic immune response to the parasite. |
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Keywords: | DP, double positive DN, double negative TUNEL, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling ABI, apoptotic body index PI, propidium iodide PS, phosphatidylserine MLN, mesenteric lymph nodes FITC, fluorescein isothiocyanate TRECs, T-cell receptor excision circles IFN-γ, interferon gamma TNF, tumor necrosis factor LT, lymphotoxin Tg, transgenic |
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