Thymic Atrophy during Infection as a Host Response to Avoid Tolerance to Persistent Pathogens
Journal Title: International Journal of TROPICAL DISEASE & Health - Year 2014, Vol 4, Issue 4
Abstract
The immune system consists in part of a functionally competent T-cell repertoire that is reactive to foreign antigens but tolerant to self-antigens. The repertoire of T cells is primarily formed in the thymus through positive and negative selection of developing thymocytes that are critical for establishing central tolerance. One of the features of the thymus is to sense stress hormones produced in pathophysiological conditions. Increased levels of these hormones are associated with infections and are able to induce thymic atrophy. We have shown that in acute Trypanosoma cruzi infections, the atrophic thymus is a consequence of increased thymocyte apoptosis and premature export of immature thymocytes to secondary lymph nodes. This atrophy does not necessarily result in dysfunction of the thymus since the organ micro architecture is preserved and maintains negative selection, thus avoiding the development of tolerance to the pathogen during the establishment of protective immunity. However, in chronic infections, the dissemination of invading pathogens able to target the thymus interferes with T cell differentiation, generating T cells that are tolerant to pathogen-specific antigens. In what follows we propose to describe what is known about thymic atrophy induced by infectious pathogens in the context of host-pathogen interactions.
Authors and Affiliations
Leonardo Santos, Eugênia Terra-Granado, Luciana Conde, Ana Flávia Nardy, Alexandre Morrot
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