The thymus as a target for mycobacterial infections

Nóbrega, Cláudia; Cardona, Père-Joan; Roque, Susana; Pinto-do-Ó, Perpétua; Appelberg, Rui; Correia-Neves, Margarida

doi:10.1016/j.micinf.2007.08.006

Cited by 41 publications

(53 citation statements)

References 26 publications

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“…Mice were sacrificed with isoflurane. The bacterial load in the organs was determined as previously described (10).…”

Section: Mice and Infectionmentioning

confidence: 99%

“…Using the mouse as a model, we previously showed that the thymus is a target for mycobacterial dissemination, regardless of whether the route of infection used is i.v. or aerogenic (10). In both cases, the bacterial load is initially undetectable or extremely low and increases progressively for several weeks postinfection (10).…”

mentioning

confidence: 99%

“…or aerogenic (10). In both cases, the bacterial load is initially undetectable or extremely low and increases progressively for several weeks postinfection (10).…”

mentioning

confidence: 99%

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Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

Nóbrega

Roque

Nunes-Alves

et al. 2009

The Journal of Immunology

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The ability of the thymus to generate a population of T cells that is, for the most part, self-restricted and self-tolerant depends to a great extent on the Ags encountered during differentiation. We recently showed that mycobacteria disseminate to the thymus, which raised the questions of how mycobacteria within the thymus influence T cell differentiation and whether such an effect impacts host–pathogen interactions. Athymic nude mice were reconstituted with thymic grafts from Mycobacterium avium-infected or control noninfected donors. T cells generated from thymi of infected donors seemed generally normal, because they retained the ability to reconstitute the periphery and to respond to unspecific stimuli in vitro as well as to antigenic stimulation with third-party Ags, such as OVA, upon in vivo immunization. However, these cells were unable to mount a protective immune response against a challenge with M. avium. The observation that thymic infection interferes with T cell differentiation, generating T cells that are tolerant to pathogen-specific Ags, is of relevance to understand the immune response during chronic persistent infections. In addition, it has potential implications for the repertoire of T cells generated in patients with a mycobacterial infection recovering from severe lymphopenia, such as patients coinfected with HIV and receiving antiretroviral therapy.

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“…Mice were sacrificed with isoflurane. The bacterial load in the organs was determined as previously described (10).…”

Section: Mice and Infectionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

Nóbrega

Roque

Nunes-Alves

et al. 2009

The Journal of Immunology

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“…Increased apoptotic index triggered by autophagic programmed cell death Thymus growth-stimulatory factor extracted from S. involvens, a fern Brito et al 2003;Gayathri et al 2011;MendesGiannini et al 2008;Savino 2006;Souto et al 2003 Bacteria Immune reaction to the thymic infection Borges et al 2012;Nobrega et al 2007Nobrega et al , 2010Reiley et al 2012 Francisella tularensis, F. tularensis an analogous patho-physiological model similar to HIVinfected human in terms of disease progression (Policicchio et al 2016). During infection of newborn rhesus macaques with SIV, ATI-associated events (including enhanced death and depletion of thymocytes by various apoptotic mechanisms) very similar to those described in HIV-infected humans (Rosenzweig et al 2000) are observed.…”

Section: Paracoccidioides Brasiliensismentioning

confidence: 99%

“…The persistent colonization by various strains of Mycobacterium tuberculosis has been reported in the thymus (Nobrega et al 2007). Moreover, spreading of Mycobacterium into the thymus caused the thymocyte population to tolerate the invading pathogens (Nobrega et al 2010).…”

Section: Bacterial Infections and Atimentioning

confidence: 99%

Acute Thymic Involution and Mechanisms for Recovery

Ansari

Liu

2017

Arch. Immunol. Ther. Exp.

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Thymus‐resident memory CD8⁺T cells mediate local immunity

et al. 2013

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T cells by antibodies further revealed that thymic virus-specific memory CD8+ T cells did not belong to the circulating pool of lymphocytes. Finally, we demonstrate that these thymus-resident virus-specific memory CD8 + T cells efficiently mounted a secondary proliferative response, exhibited immediate effector functions and were able to protect the thymus from lymphocytic choriomeningitis virus reinfection. In conclusion, the present study not only describes for the first time virus-specific memory CD8 + T cells with characteristics of tissue-resident memory T (T RM ) cells in a primary lymphoid organ but also extends our knowledge about local T-cell immunity in the thymus.Keywords: CD69 r CD103 r E-cadherin r Tissue-resident memory T (T RM ) cells r Viral infections See accompanying Commentary by Mackay and GebhardtAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionCirculating memory T cells are usually separated into two main populations defined by their expression of lymph node homing molecules: central memory T (T CM ) cells and effector memory T (T EM ) cells [1]. T CM cells have a high proliferative potential and express CCR7/CD62L that allows them to traffic between the secondary lymphoid organs to maintain the memory T-cell pool. T EM cells lack lymph node homing receptors and circulate between Correspondence: Prof. Hanspeter Pircher e-mail: hanspeter.pircher@uniklinik-freiburg.de the blood and extralymphoid organs to patrol the body [2]. Some regions in the body, however, are excluded from immune surveillance by circulating memory T cells, namely peritoneal cavity, gut, and brain as shown by parabiosis experiments [3]. More recently, a third main memory T-cell population that persists in peripheral organs after viral infections to secure immediate local defense after pathogen reencounter has been identified in humans and mice [4,5]. These memory T cells are called tissue-resident memory T cells (T RM cells) and are not replenished from the circulation. Beside the lack of recirculation, the expression of CD103 and CD69 and local antigen-independent persistence are characteristics of T RM cells [4]. T RM cells have so far been described in Eur. J. Immunol. 2013. 43: 2295-2304 the gut, skin, brain, sensory ganglia, vagina, lungs, and salivary glands [4,[6][7][8][9][10]. These tissues are mostly surface lining and either epithelial or neuronal derived with anatomical border layers like basement membranes or the blood-brain barrier, and therefore, more difficult to be patrolled by circulating cells. Another epithelial-derived organ is the thymus, a primary lymphoid organ in which T-cell differentiation takes place [11]. During maturation, T cells undergo positive and negative selection eliminating useless and most harmful T cells. These selection processes depend on TCR interactions with self-MHC molecules presenting peptide antigens expressed in the thymus. Therefore, the expression of antigen within the thymus has to be tightly con...

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The thymus as a target for mycobacterial infections

Cited by 41 publications

References 26 publications

Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

Acute Thymic Involution and Mechanisms for Recovery

Thymus‐resident memory CD8⁺T cells mediate local immunity

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The thymus as a target for mycobacterial infections

Cited by 41 publications

References 26 publications

Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

Acute Thymic Involution and Mechanisms for Recovery

Thymus‐resident memory CD8+T cells mediate local immunity

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Product

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Thymus‐resident memory CD8⁺T cells mediate local immunity