Cutting Edge: STAT1 and T-bet Play Distinct Roles in Determining Outcome of Visceral Leishmaniasis Caused by<i>Leishmania donovani</i>

Rosas, Lucia E.; Snider, Heidi; Barbi, Joseph; Satoskar, Anjali A.; Lugo-Villarino, Geanncarlo; Keiser, Tracy L.; Papenfuss, Tracy; Durbin, Joan E.; Radzioch, Danuta; Glimcher, Laurie H.; Satoskar, Abhay R.

doi:10.4049/jimmunol.177.1.22

Cited by 49 publications

(61 citation statements)

References 28 publications

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“…Ϫ/Ϫ mice failed to establish Leishmania donovani infection due to proposed defects in STAT1-deficient macrophage trafficking to the liver (61). Taken together, our data support a requirement for STAT1 in DCs to provide the necessary factors, both Ag presentation machinery and cytokines, to initiate Th1 cell development.…”

Section: Discussionmentioning

confidence: 52%

STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity toLeishmania major

Johnson

Scott

2007

The Journal of Immunology

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The generation of Th1 responses is important for resistance to intracellular pathogens, including the parasite, Leishmania major. Although IFN-γR/STAT1 signaling promotes a Th1 response via the up-regulation of T-bet, the requirement for STAT1 in Th1 cell differentiation remains controversial. Although in some cases Th1 cells develop independently of STAT1, STAT1−/− mice fail to develop a Th1 response during L. major infection. However, the interpretation of this result is complicated by the role STAT1 plays in Ag presentation and, more importantly, in elimination of parasites by macrophages, because both defective Ag presentation and increased parasite burden can influence Th cell development. To resolve this issue, we assessed the ability of STAT1−/− T cells to become Th1 cells and protect mice against L. major following adoptive transfer into STAT1-sufficient mice. We found that whereas T-bet is critical for the differentiation of protective Th1 cells during L. major infection, IFN-γR and STAT1 are dispensable. Given that a STAT1-independent Th1 cell response was generated by STAT1-sufficient APCs, but not by STAT1−/− cells, we next addressed whether dendritic cells (DCs) require STAT1 signaling to effectively present Ag. We found that STAT1−/− DCs had impaired up-regulation of MHC and costimulatory molecules, and, as a consequence, the absence of STAT1 resulted in reduced Th1 cell priming. Taken together, these results demonstrate that T cell expression of STAT1 is not required for the development of Th1 cells protective against L. major and instead stress the importance of STAT1 signaling in DCs for the optimal induction of Th1 responses.

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Section: Discussionmentioning

confidence: 52%

STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity toLeishmania major

Johnson

Scott

2007

The Journal of Immunology

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“…The same trend was observed in a model of Leishmania donovani infection, where T-bet deficient mice had high parasitic loads and failed to develop a Th1 response (Rosas et al, 2006). Similar to Leishmania infection, T-bet-/-mice are unable to control infection with Staphylococcus aureus, due to impaired CD4+ T cell responses and decreased IFN-γ production (Hultgren et al, 2004).…”

Section: Bacterial and Parasitic Infectionsmentioning

confidence: 58%

Role of IFN-α/β signaling in the prevention of genital herpes virus type 2 infection

Svensson

Bellner

Magnusson

et al. 2007

Journal of Reproductive Immunology

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Genital herpes, caused by herpes simplex virus type 2 (HSV-2), is the most common genital ulcer disease worldwide. HSV-2 infection causes a variety of symptoms, ranging from subclinical/silent infection to severe and recurrent episodes of genital blisters and ulcers, and the virus can also in rare cases cause meningitis. In primary infection, the virus sequentially enters and replicates in epithelial cells followed by local sensory neurons. In the latter, a life-long infection is established via the induction of viral latency or dormancy. Latent virus is however continuously reactivated, also in those with a silent infection, which results in a low-grade viral replication and shedding into the vaginal lumen. This reactivation can in many individuals be amplified following e.g. stress, hormonal variations or immune suppression, which results in recurrent genital disease.

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“…The outcomes of challenge infections in BALB/c mice following vaccination via four different routes with LAg and LAg in liposomes were evaluated. In contrast to selflimiting infection (26,29), inoculation of BALB/c mice with L. donovani strain AG83 leads to progressive infection in the liver and spleen, corresponding with hepato-and splenomegaly (2,7,19,24). Figure 1A shows that mice vaccinated with LAg through the i.p.…”

Section: Resultsmentioning

confidence: 99%

Vaccination Route That Induces Transforming Growth Factor β Production Fails To Elicit Protective Immunity againstLeishmania donovaniInfection

2009

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Cutting Edge: STAT1 and T-bet Play Distinct Roles in Determining Outcome of Visceral Leishmaniasis Caused byLeishmania donovani

Cited by 49 publications

References 28 publications

STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity toLeishmania major

STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity toLeishmania major

Role of IFN-α/β signaling in the prevention of genital herpes virus type 2 infection

Vaccination Route That Induces Transforming Growth Factor β Production Fails To Elicit Protective Immunity againstLeishmania donovaniInfection

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