Role of host phosphotyrosine phosphatase SHP-1 in the development of murine leishmaniasis
- 1 November 2001
- journal article
- Published by Wiley in European Journal of Immunology
- Vol. 31 (11), 3185-3196
- https://doi.org/10.1002/1521-4141(200111)31:11<3185::aid-immu3185>3.0.co;2-j
Abstract
Activation of host phosphotyrosine phosphatase SHP‐1 by Leishmania and its subsequent impact on tyrosine phosphorylation‐based signaling cascades were shown to represent an important mechanism whereby this pathogen may alter host cell functions. Herein, we report that Leishmania‐induced macrophage SHP‐1 activity is necessary for its survival within phagocytes through the attenuation of nitric oxide‐dependent and ‐independent microbicidal mechanisms. In vivo, Leishmania major infection, which footpad inflammation is mostly undetectable in SHP‐1‐deficient viable motheaten mice, was accompanied by increased inducible nitric oxide synthase and activation of neutrophils. These enhanced cellular activities were paralleled by a marked activation of signaling events usually negatively regulated by SHP‐1. Overall, this study firmly establishes that modulation of the signaling terminator SHP‐1 by Leishmania is essential for its installment and propagation.Keywords
This publication has 35 references indexed in Scilit:
- Leishmania-induced increases in activation of macrophage SHP-1 tyrosine phosphatase are associated with impaired IFN-γ-triggered JAK2 activationEuropean Journal of Immunology, 1999
- NITRIC OXIDE AND MACROPHAGE FUNCTIONAnnual Review of Immunology, 1997
- Modulation of host cell intracellular Ca2+Parasitology Today, 1996
- Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice.The Journal of Experimental Medicine, 1996
- Regulation of Cytokine-inducible Nitric Oxide Synthase in Cardiac Myocytes and Microvascular Endothelial Cells: ROLE OF EXTRACELLULAR SIGNAL-REGULATED KINASES 1 AND 2 (ERK1/ERK2) AND STAT1αPublished by Elsevier BV ,1996
- Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthaseCell, 1995
- The Regulation of Immunity to Leishmania MajorAnnual Review of Immunology, 1995
- Expression and catalytic activity of the tyrosine phosphatase PTP1C is severely impaired in motheaten and viable motheaten mice.The Journal of Experimental Medicine, 1993
- Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase geneNature Genetics, 1993
- Estimation of population at risk of infection and number of cases of LeishmaniasisParasitology Today, 1992