Altered bone marrow lymphopoiesis and interleukin-6-dependent inhibition of thymocyte differentiation contribute to thymic atrophy during  Trypanosoma cruzi infection

Sofía Carbajosa; Susana Gea; Carlos Chillón-Marinas; Cristina Poveda; María del Carmen Maza; Manuel Fresno; Núria Gironès

doi:10.18632/oncotarget.14886

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Research Papers: Immunology:

Altered bone marrow lymphopoiesis and interleukin-6-dependent inhibition of thymocyte differentiation contribute to thymic atrophy during Trypanosoma cruzi infection

Sofía Carbajosa, Susana Gea, Carlos Chillón-Marinas, Cristina Poveda, María del Carmen Maza, Manuel Fresno and Núria Gironès _

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Oncotarget. 2017; 8:17551-17561. https://doi.org/10.18632/oncotarget.14886

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Abstract

Sofía Carbajosa1, Susana Gea2, Carlos Chillón-Marinas1, Cristina Poveda1, María del Carmen Maza1,3, Manuel Fresno1,3,* and Núria Gironès1,3,*

1 Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain

2 Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina

3 Instituto Sanitario de Investigación Princesa, Madrid, Spain

* These authors have equally contributed to the direction of this work

Correspondence to:

Núria Gironès, email:

Keywords: thymic atrophy; interleukin-6; glucocorticoids; Trypanosoma cruzi infection; Chagas disease; Immunology and Microbiology Section; Immune response; Immunity

Received: March 17, 2016 Accepted: January 17, 2017 Published: January 28, 2017

Abstract

Thymic atrophy occurs during infection being associated with apoptosis of double positive (DP) and premature exit of DP and double negative (DN) thymocytes. We observed for the first time that a significant bone marrow aplasia and a decrease in common lymphoid progenitors (CLPs) preceded thymic alterations in mice infected with Trypanosoma cruzi. In addition, depletion of the DN2 stage was previous to the DN1, indicating an alteration in the differentiation from DN1 to DN2 thymocytes. Interestingly, infected mice deficient in IL-6 expression showed higher numbers of DP and CD4+ thymocytes than wild type infected mice, while presenting similar percentages of DN1 thymocytes. Moreover, the drop in late differentiation stages of DN thymocytes was partially abrogated in comparison with wild type littermates. Thus, our results suggest that thymic atrophy involves a drop in CLPs production in bone marrow and IL-6-dependent and independent mechanisms that inhibits the differentiation of DN thymocytes.

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Research Papers: Immunology:

Altered bone marrow lymphopoiesis and interleukin-6-dependent inhibition of thymocyte differentiation contribute to thymic atrophy during Trypanosoma cruzi infection

Abstract