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Author(s): Margarida Borges
Palmira Barreira Silva
Manuela Florido
Michael B Jordan
Margarida Correia Neves
Rui Appelberg
Title: Molecular and Cellular Mechanisms of Mycobacterium avium-Induced Thymic Atrophy
Issue Date: 2012
Abstract: Thymic atrophy has been described as a consequence of infection by several pathogens and shown to be induced through diverse mechanisms. Using the mouse model of Mycobacterium avium infection, we show in this study that the production of NO from IFN-gamma-activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low-virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFN-gamma or the inducible NO synthase. In addition, mice with a selective impairment of IFN-gamma signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain, and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and/or during the differentiation of these cells in the bone marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced NO, endogenous corticosteroid activity, and reduced bone marrow seeding. The Journal of Immunology, 2012, 189: 3600-3608.
Subject: Imunologia, Medicina básica
Immunology, Basic medicine
Scientific areas: Ciências médicas e da saúde::Medicina básica
Medical and Health sciences::Basic medicine
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:FFUP - Artigo em Revista Científica Internacional
ICBAS - Artigo em Revista Científica Internacional

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