Interleukin-17-Mediated Control of Parasitemia in Experimental<i>Trypanosoma congolense</i>Infection in Mice

Mou, Zhirong; Jia, Ping; Kuriakose, Shiby; Khadem, Forough; Uzonna, Jude E.

doi:10.1128/iai.00168-10

Cited by 18 publications

(10 citation statements)

References 50 publications

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“…In addition to its impact in bacterial and fungal infections, emerging data implicate IL-17 in the control of selected parasitic pathogens 3–5 . Consistent with this theme, recent work has suggested an important role for IL-17 in resolution of infection with the protozoan parasites, Trypanosoma cruzi ( T. cruzi ) and Trypanosoma congolense 6–8 . Indeed, prior work from our group indicates that IL-17 exerts its protective function following exposure of mice to T. cruzi , in part, by recruiting suppressive IL-10–producing neutrophils that modulate interferon-γ (IFN-γ) production and thereby limit tissue damage 9 .…”

mentioning

confidence: 66%

Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells

et al. 2013

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We identified B cells as a major source for rapid, innate-like interleukin 17 (IL-17) production in vivo in response to Trypanosoma cruzi infection. IL-17+ B cells exhibited a plasmablast phenotype, outnumbered TH17 cells and were required for optimal response to this pathogen. Using both murine and human primary B cells, we demonstrate that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell surface mucin, CD45, leading to Btk-dependent signaling and IL-17A or IL-17F production via an ROR-γt and AHR-independent transcriptional program. Our combined data suggest that generation of IL-17+ B cells may be an unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.

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mentioning

confidence: 66%

Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells

et al. 2013

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“…Nitrite concentration in the culture supernatants was measured by using Griess reagent as previously described [19]. Briefly, ANA-1 and BALB.BM cell monolayers were stimulated with TC, IFN-γ (500 IU/ml), or both and at indicated times, the supernatants were centrifuged at 1200 rpm for 10 min to remove cellular debris and the concentration of nitrite in the supernatant fluids was determined.…”

Section: Methodsmentioning

confidence: 99%

Molecular Regulation of Trypanosoma congolense-Induced Nitric Oxide Production in Macrophages

Singh

Kone²,

Gounni

et al. 2013

PLoS ONE

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BALB/c mice are highly susceptible while C57BL/6 mice are relatively resistant to experimental Trypanosoma congolense infection. Several reports show that an early interferon-gamma (IFN-γ) response in infected mice is critically important for resistance via the activation of macrophages and production of nitric oxide (NO). NO is a pivotal effector molecule and possesses both cytostatic and cytolytic properties for the parasite. However, the molecular mechanisms leading to T. congolense (TC)-induced NO release from macrophages are not known. In this study, we investigated the signaling pathways induced by trypanosomes in immortalized macrophage cell lines from the highly susceptible BALB/c (BALB.BM) and relatively resistant C57Bl/6 (ANA-1) mice. We found that T. congolense whole cell extract (TC-WCE) induces significantly higher levels of NO production in IFN-γ-primed ANA-1 than BALB.BM cells, which was further confirmed in primary bone marrow-derived macrophage (BMDM) cultures. NO production was dependent on mitogen-activated protein kinase (MAPK, including p38, Erk1/2, and JNK) phosphorylation and was significantly inhibited by specific MAPK inhibitors in BALB.BM, but not in ANA-1 cells. In addition, T. congolense- and IFN-γ-induced NO production in ANA-1 and BALB.BM cells was dependent on STAT1 phosphorylation and was totally suppressed by the use of fludarabine (a specific STAT1 inhibitor). We further show that T. congolense induces differential iNOS transcriptional promoter activation in IFN-γ-primed cells, which is dependent on the activation of both GAS1 and GAS2 transcription factors in BALB.BM but only on GAS1 in ANA-1 cells. Taken together, our findings show the existence of differential signalling events that lead to NO production in macrophages from the highly susceptible and relatively resistant mice following treatment with IFN-γ and T. congolense. Understanding these pathways may help identify immunomodulatory mechanisms that regulate the outcome of infection during Trypanosome infections.

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“…However, their protective function in various infectious diseases has also been reported (Mou et al, 2010; Wu et al, 2010). T cells from infected susceptible BALB/c mice produce more IL-17 than those from the resistant C57BL/6 mice and L. major -infected IL-17 deficient BALB/c mice develop smaller lesions and harbor lower parasites compared to their WT counterpart mice (Lopez Kostka et al, 2009).…”

Section: Role Of Cytokinesmentioning

confidence: 99%

“…T helper 17 (Th17) cells are new T helper cell subsets that produce interleukin IL-17A (also called IL-17), a pro-inflammatory cytokine that play important pathologic role in several immune-mediated disease (Chang et al, 2011 ; Zhang et al, 2011 ). However, their protective function in various infectious diseases has also been reported (Mou et al, 2010 ; Wu et al, 2010 ). T cells from infected susceptible BALB/c mice produce more IL-17 than those from the resistant C57BL/6 mice and L. major -infected IL-17 deficient BALB/c mice develop smaller lesions and harbor lower parasites compared to their WT counterpart mice (Lopez Kostka et al, 2009 ).…”

Section: Role Of Cytokinesmentioning

confidence: 99%

Protective Immunity and Vaccination Against Cutaneous Leishmaniasis

Okwor¹,

Mou²,

Liu³

et al. 2012

Front. Immun.

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Although a great deal of knowledge has been gained from studies on the immunobiology of leishmaniasis, there is still no universally acceptable, safe, and effective vaccine against the disease. This strongly suggests that we still do not completely understand the factors that control and/or regulate the development and sustenance of anti-Leishmania immunity, particularly those associated with secondary (memory) immunity. Such an understanding is critically important for designing safe, effective, and universally acceptable vaccine against the disease. Here we review the literature on the correlate of protective anti-Leishmania immunity and vaccination strategies against leishmaniasis with a bias emphasis on experimental cutaneous leishmaniasis.

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Interleukin-17-Mediated Control of Parasitemia in ExperimentalTrypanosoma congolenseInfection in Mice

Cited by 18 publications

References 50 publications

Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells

Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells

Molecular Regulation of Trypanosoma congolense-Induced Nitric Oxide Production in Macrophages

Protective Immunity and Vaccination Against Cutaneous Leishmaniasis

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