Altered bone marrow lymphopoiesis and interleukin-6-dependent inhibition of thymocyte differentiation contribute to thymic atrophy during Trypanosoma cruzi infection.
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.
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Sofía
S
Carbajosa
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Susana
S
Gea
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Carlos
C
Chillón-Marinas
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Cristina
C
Poveda
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.|Instituto Sanitario de Investigación Princesa, Madrid, Spain.
María
M
Del Carmen Maza
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.|Instituto Sanitario de Investigación Princesa, Madrid, Spain.
Manuel
M
Fresno
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.|Instituto Sanitario de Investigación Princesa, Madrid, Spain.
Núria
N
Gironès
D000818:Animals; D001284:Atrophy; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000378:metabolism*; D054503:Lymphoid Progenitor Cells / Q000166:cytology; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060168:Thymocytes / Q000473:pathology*; D013950:Thymus Gland / Q000473:pathology*; D014349:Trypanosoma cruzi
D015850:Interleukin-6
Chagas disease; Immune response; Immunity; Immunology and Microbiology Section; Trypanosoma cruzi infection; glucocorticoids; interleukin-6; thymic atrophy