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Experimental Visceral Leishmaniasis (experimental + visceral_leishmaniasis)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Signaling events leading to the curative effect of cystatin on experimental visceral leishmaniasis: Involvement of ERK1/2, NF-,B and JAK/STAT pathways

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2009
Susanta Kar
Abstract Curative effect of cystatin, a natural cystein protease inhibitor, on experimental visceral leishmaniasis was associated with strong upregulation of iNOS. The transductional mechanisms underlying this cellular response was investigated in the murine macrophage cell line RAW 264.7 and in the BALB/c mouse model of visceral leishmaniasis. Cystatin synergizes with IFN-, in inducing ERK1/2 phosphorylation and NF-,B DNA-binding activity. Pretreatment of cells with specific inhibitors of NF-,B or ERK1/2 pathway blocked the cystatin plus IFN-,-inducible NF-,B activity and markedly reduced the expression of iNOS at both mRNA and protein levels. Silencing of mitogen- and stress-activated protein kinase 1 significantly reduced cystatin-mediated NF-,B-dependent iNOS gene transcription suggesting the involvement of mitogen- and stress-activated protein kinase 1 activation in ERK1/2 signaling. DNA binding as well as silencing experiments revealed the requirement of IFN-,-mediated JAK-STAT activation even though cystatin did not modulate this signaling cascade by itself. In the in vivo situation, key steps in the activation cascade of NF-,B, including nuclear translocation of NF-,B subunits, I,B phosphorylation and I,B kinase, are all remarkably enhanced in Leishmania -infected mice by cystatin. Understanding the molecular mechanisms through which cystatin modulates macrophage effector responses will contribute to better define its potential for macrophage-associated diseases, in general. [source]

Tissue granuloma structure-function in experimental visceral leishmaniasis

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2001
Henry W. Murray
In experimental visceral leishmaniasis in normal mice (BALB/c, C57BL/6) acquired resistance to Leishmania donovani, a protozoan which targets tissue macrophages, depends upon T cells, Th1 cell-type cytokine generation and activated mononuclear phagocytes. In the intact host, initial control and eventual resolution of L. donovani hepatic infection in normal mice is expressed by and accomplished within well-formed, mature tissue granulomas. In the liver, these immunologically active, inflammatory structures are assembled around a core of fused, parasitized resident macrophages (Kupffer cells) which come to be encircled by both cytokine-secreting T cells and influxing leishmanicidal blood monocytes. This pro-host defense granuloma structure-function relationship, in which histologically mature granulomas provide the microenvironment for intracellular L. donovani killing, however, is only one of seven which have been identified through experimental modifications in this model. This report reviews these structure-function relationships and illustrates the broad spectrum of additional possible responses. These responses range from structurally intact granulomas which provide no antileishmanial function (the ,ineffective' granuloma), to enlarged granulomas which show enhanced parasite killing (the ,hypertrophied' granuloma), to effective antileishmanial activity in the absence of any tissue reaction (the ,invisible' granuloma). [source]