Browsing by Author "Magez, Stefan"

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    Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection
    (Public Library of Science, 2007) Radwanska, Magdalena; Cutler, Antony J; Hoving, J Claire; Magez, Stefan; Holscher, Christoph; Bohms, Andreas; Arendse, Berenice; Kirsch, Richard; Hunig, Thomas; Alexander, James
    Author Summary Leishmaniasis is a disease induced by a protozoan parasite and transmitted by the sandfly. Several forms of infection are identified, and the different diseases have wide-ranging symptoms from localized cutaneous sores to visceral disease affecting many internal organs. Animal models of human cutaneous leishmaniasis have been established in which disease is induced by infecting mice subcutaneously with Leishmania major. Different strains of inbred mice have been found to be susceptible or resistant to L. major infection. "Healer" C57BL/6 mice control infection with transient lesion development. The protective response to infection in this strain is dominated by type 1 cytokines inducing parasite killing by nitric oxide. Conversely, "nonhealer" BALB/c mice are unable to control infection and develop nonhealing lesions associated with a dominant type 2 immune response driven by cytokines IL-4 and IL-13. However, mice deficient in IL-4/IL-13 signaling are not protected against development of cutaneous leishmaniasis. Here we describe a BALB/c mouse where the ability to polarize to a dominant type 2 response is removed by cell-specific deletion of the receptor for IL-4/IL-13 on CD4 + T cells. These mice are resistant to L. major infection similar to C57BL/6 mice, which highlights the role of T helper 2 cells in driving susceptibility and the protective role of IL-4/IL-13 signaling in non-CD4 + T cells in BALB/c mice.
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    Mycobacterium tuberculosis and trypanosoma brucei as models for the TLR-dependent activation of the innate immune system
    (2005) Drennan, Michael B; Ryffel, Bernhard; Magez, Stefan
    Includes bibliographical references.
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    NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia
    (Public Library of Science, 2015) Cnops, Jennifer; Trez, Carl De; Stijlemans, Benoit; Keirsse, Jiri; Kauffmann, Florence; Barkhuizen, Mark; Keeton, Roanne; Boon, Louis; Brombacher, Frank; Magez, Stefan
    African trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia.
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    The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice
    (Public Library of Science, 2008) Magez, Stefan; Schwegmann, Anita; Atkinson, Robert; Claes, Filip; Drennan, Michael; De Baetselier, Patrick; Brombacher, Frank
    Author Summary African trypanosomiasis is a disease caused by different species of extracellular flagellated protozoan trypanosome parasites. Trypanosomes have developed a mechanism of regular antigenic variation of their variant-specific surface glycoprotein (VSG) coat which allows chronic infection. Replacement of this coat occurs at rapid regular time intervals, allowing the parasite to escape from an effective host antibody responses. So far, primary T-cell independent antibody responses have been described to constitute the main host defense mechanism, relying largely on IgM antibody induction. Using genetically engineered B lymphocyte- or IgM-deficient mouse strains, we show that lack of B-cells or IgM did not prevent infection-associated anemia. More importantly, we show that in the absence of IgM, parasitemia was controlled almost as well as in wild-type mice, with only slightly increased mortality. In addition, we show in vivo that antigenic variation is not affected by the lack of IgM.