Interferon‐γ‐ and glucocorticoid‐mediated pathways synergize to enhance death of CD4+ CD8+ thymocytes during Salmonella enterica serovar Typhimurium infection

Deobagkar-Lele, Mukta; Chacko, Suni K.; Victor, Emmanuel S.; Kadthur, Jayachandra C.; Nandi, Dipankar

doi:10.1111/imm.12047

Cited by 36 publications

(91 citation statements)

References 60 publications

(154 reference statements)

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“…5a). IFN-c was shown to participate in the induction of thymic atrophy and T-cell depletion during viral and bacterial infections, such as severe influenza A(H1N1)pdm09, Salmonella enteric serovar Typhimurium, and Mycobacterium avium (Borges et al, 2012;Deobagkar-Lele et al, 2013;Liu et al, 2014). We showed directly that IFN-c increased the apoptosis of thymocytes using an in vitro culture experiment (Fig.…”

Section: Discussionmentioning

confidence: 80%

“…versus mock-infected). IFN-c is a key cytokine involved in the protective immune response against various pathogen infections (Flynn et al, 1993;Julkunen et al, 2001), but has also been shown to participate in the induction of pathological courses, especially thymic atrophy and T-cell depletion during viral or bacterial infections (Borges et al, 2012;Deobagkar-Lele et al, 2013;Liu et al, 2014).…”

Section: Nk-cells Were Activated By Influenza Virus Infectionmentioning

confidence: 99%

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NK-cells are involved in thymic atrophy induced by influenza A virus infection

Duan

Zhou

et al. 2015

Journal of General Virology

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NK-cells have traditionally been viewed as innate effector lymphocytes that serve as a first line of defence against a range of viruses and tumours. More recently, the importance of NK-cell immunoregulatory functions has been highlighted. NK-cells can inhibit antiviral T-cell responses, and also play an important role in controlling harmful T-cell activity in autoimmunity and transplantation settings. Moreover, immunopathological effects of NK-cells during infection have been reported. Nevertheless, the phenotype and function of NK-cells in the thymus during influenza virus infection is not understood. In the present study, we demonstrated that influenza A virus (IAV) infection in mice led to severe thymic atrophy caused by increased thymic T-cell apoptosis and suppressed proliferation. We found that NK-cells played a critical role in this phenotype. IFN-c production by NK-cells was a contributing factor for thymic atrophy during IAV infection. Taken together, our data indicate that NK-cells are involved in the thymic atrophy associated with IAV infection.

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Section: Discussionmentioning

confidence: 80%

Section: Nk-cells Were Activated By Influenza Virus Infectionmentioning

confidence: 99%

NK-cells are involved in thymic atrophy induced by influenza A virus infection

Duan

Zhou

et al. 2015

Journal of General Virology

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“…Other inflammatory mediators may rise during infection, leading to thymic damage, and again in particular depletion of the DP population. These include tumour necrosis factor α, the release of which can be triggered by infection with Francisella tularenis (46) and Trypanosoma cruzi infection (47); as well as the release of interferon γ caused by Salmonella enterica infection (48). …”

Section: Causes and Targets Of Acute Thymic Damagementioning

confidence: 99%

Thymus: the next (re)generation

Chaudhry

Velardi

Dudakov

et al. 2016

Immunological Reviews

141

131

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Summary As the primary site of T cell development, the thymus plays a key role in the generation of a strong yet self-tolerant adaptive immune response, essential in the face of the potential threat from pathogens or neoplasia. As the importance of the role of the thymus has grown, so too has the understanding that it is extremely sensitive to both acute and chronic injury. The thymus undergoes rapid degeneration following a range of toxic insults, and also involutes as part of the aging process, albeit at a faster rate than many other tissues. The thymus is, however, capable of regenerating, restoring its function to a degree. Potential mechanisms for this endogenous thymic regeneration include keratinocyte growth factor (KGF) signaling, and a more recently described pathway in which innate lymphoid cells produce interleukin-22 (IL-22) in response to loss of double positive thymocytes and upregulation of IL-23 by dendritic cells. Endogenous repair is unable to fully restore the thymus, particularly in the aged population, and this paves the way towards the need for exogenous strategies to help regenerate or even replace thymic function. Therapies currently in clinical trials include KGF, use of the cytokines IL-7 and IL-22, and hormonal modulation including growth hormone administration and sex steroid inhibition. Further novel strategies are emerging in the pre-clinical setting, including the use of precursor T cells and thymus bioengineering. The use of such strategies offers hope that for many patients, the next regeneration of their thymus is a step closer.

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“…Furthermore, inhibition of the endogenous corticosteroid signaling partially reversed the atrophy of the thymus whereas enhancement of endogenous host-encoded IFN-γ participated in the apoptosis of the DP thymocytes. Moreover, interactions between these two key pathways led to an additive effect on the reduction in the DP thymocyte survival (Deobagkar-Lele et al 2013). More recently, a skewed process of thymocyte development was detected during S. typhimurium-induced ATI as a primary event that caused continuous development of thymocytes leading to a set of SP thymocyte clones that exhibited a unique T cell receptor β chain (TCR-Vβ), which was independent of the changes in thymic architecture during the course of the infection.…”

Section: Bacterial Infections and Atimentioning

confidence: 99%