Signal transducer and activator of transcription 1 in T cells plays an indispensable role in immunity to
            <i>Leishmania major</i>
            by mediating Th1 cell homing to the site of infection

Barbi, Joseph; Snider, Heidi; Bhardwaj, Neeti; Lezama-Dávila, Claudio M.; Durbin, Joan E.; Satoskar, Abhay R.

doi:10.1096/fj.09-138057

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…Studies using STAT1 KO mice have implicated a role for STAT1 in both lymphocyte proliferation and migration (47)(48)(49). To address whether the absence of STAT1 affected the timing or magnitude of T cell infiltration into the infected brain parenchyma, immune cell profiles were determined in brain tissues of MV-infected NSE-CD46 + and NSE-CD46 + /STAT1-KO mice by flow cytometry and immunohistochemistry.…”

Section: T Cell Infiltration Into the Cns And Control And Clearance Omentioning

confidence: 99%

STAT1-Independent Control of a Neurotropic Measles Virus Challenge in Primary Neurons and Infected Mice

O’Donnell

Conway

Rose

et al. 2012

The Journal of Immunology

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Neurons are chiefly non-renewable; thus, cytolytic immune strategies to clear or control neurotropic viral infections could have lasting neurological consequences. Interferon-gamma (IFNγ) is a potent anti-viral cytokine that is critical for non-cytolytic clearance of multiple neurotropic viral infections, including measles virus (MV); however, the downstream pathways through which IFNγ functions in neurons have not been defined. Unlike most cell types studied to date in which IFNγ affects gene expression via rapid and robust activation of STAT1, basal STAT1 levels in primary hippocampal neurons are constitutively low, resulting in attenuated STAT1 activation and consequently slower kinetics of IFNγ-driven STAT1-dependent gene expression. Given this altered expression and activation of STAT1 in neurons, we sought to determine whether STAT1 was required for IFNγ-mediated protection from infection in neurons. To do so, we evaluated the consequences of MV challenge of STAT1-deficient mice and primary hippocampal neurons explanted from these mice. Surprisingly, the absence of STAT1 did not restrict the ability of IFNγ to control viral infection either in vivo or ex vivo. Moreover, the canonical IFNγ-triggered STAT1 gene expression profile was not induced in STAT1-deficient neurons, suggesting that IFNγ regulates neuronal STAT1-independent pathways to control viral replication.

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Section: T Cell Infiltration Into the Cns And Control And Clearance Omentioning

confidence: 99%

STAT1-Independent Control of a Neurotropic Measles Virus Challenge in Primary Neurons and Infected Mice

O’Donnell

Conway

Rose

et al. 2012

The Journal of Immunology

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“…However, the mechanism of inhibition of STAT1 by Leishmania may be even more complex as another study found that L. donovani, L. major and L. mexicana trigger the specific degradation of STAT1 by the proteasome; indeed, infection by the parasite was significantly inhibited by the addition of proteasome inhibitors to infected cells [213], raising the question of whether there can be specific targeting of STAT1a and not of STAT1b for the proteasome. The contribution of STAT1 to resistance to L. major appears to be an upregulation of CXCR3, which stimulates the migration of Th1 cells to the infection site [214]. In fact, another species, Leishmania amazonensis, was shown recently to efficiently downregulate the activation pathway of several cytokines, including IFNg, by inducing decreased phosphorylation of STAT1, STAT2 and STAT3 and also specific degradation of STAT2 [215]-an action that is prevented by proteasome inhibitors.…”

Section: Inhibition Of Stat1 Phosphorylationmentioning

confidence: 99%

STAT1 and pathogens, not a friendly relationship

2010

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STAT1 belongs to the STAT family of transcription factors, which comprises seven factors: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B and STAT6. STAT1 is a 91 kDa protein originally identified as the mediator of the cellular response to interferon (IFN) alpha, and thereafter found to be a major component of the cellular response to IFNgamma. STAT1 is, in fact, involved in the response to several cytokines and to growth factors. It is activated by cytokine receptors via kinases of the JAK family. STAT1 becomes phosphorylated and forms a dimer which enters the nucleus and triggers the transcription of its targets. Although not lethal at birth, selective gene deletion of STAT1 in mice leads to rapid death from severe infections, demonstrating its major role in the response to pathogens. Similarly, in humans who do not express STAT1, there is a lack of resistance to pathogens leading to premature death. This indicates a key, non-redundant function of STAT1 in the defence against pathogens. Thus, to successfully infect organisms, bacterial, viral or parasitic pathogens must overcome the activity of STAT1, and almost all the steps of this pathway can be blocked or inhibited by proteins produced in infected cells. Interestingly, some pathogens, like the oncogenic Epstein-Barr virus, have evolved a strategy which uses STAT1 activation.

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“…62 In contrast, Barbi and colleagues demonstrated that STAT1 signaling in CD4 C T cells is essential for the development of an antimicrobial state against L. major, whereas it is not essential in CD8 C T cells. 63 Additional results have suggested that STAT1 expression is critical for preventing systemic dissemination of parasite infection, most probably by controlling the migration of Th1 cells to sites of inflammation rather than their generation. 63 …”

Section: Lessons Learned From Other Kinetoplastidsmentioning

confidence: 99%

“…63 Additional results have suggested that STAT1 expression is critical for preventing systemic dissemination of parasite infection, most probably by controlling the migration of Th1 cells to sites of inflammation rather than their generation. 63 …”

Section: Lessons Learned From Other Kinetoplastidsmentioning

confidence: 99%

Trypanosoma cruziparasites fight for control of the JAK-STAT pathway by disarming their host

et al. 2014

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The zoonotic Chagas' disease is caused by infections with the hemoflagellate Trypanosoma cruzi (T. cruzi) which is endemic in Latin America. Despite recent advances in our understanding of the pathogenesis of the disease, the underlying molecular processes involved in host-parasite interactions are only poorly understood. In particular, the mechanisms for parasite persistence in host cells remain largely unknown. Cytokine-driven transcription factors from the family of STAT (signal transducer and activator of transcription) proteins appear to play a central role in the fight against T. cruzi infection. However, amastigotes proliferating in the cytoplasm of infected host cells develop effective strategies to circumvent the attack executed by STAT proteins. This review highlights the interactions between T. cruzi parasites and human host cells in terms of cytokine signaling and, in particular, discusses the impact of STATs on the balance between parasite invasion and clearance.

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Signal transducer and activator of transcription 1 in T cells plays an indispensable role in immunity to Leishmania major by mediating Th1 cell homing to the site of infection

Cited by 14 publications

References 27 publications

STAT1-Independent Control of a Neurotropic Measles Virus Challenge in Primary Neurons and Infected Mice

STAT1-Independent Control of a Neurotropic Measles Virus Challenge in Primary Neurons and Infected Mice

STAT1 and pathogens, not a friendly relationship

Trypanosoma cruziparasites fight for control of the JAK-STAT pathway by disarming their host

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