Role of host phosphotyrosine phosphatase SHP‐1 in the development of murine leishmaniasis

• Published in: European journal of immunology Vol. 31; no. 11; pp. 3185 - 3196
• Main Authors: Forget, Geneviève, Siminovitch, Katherine A., Brochu, Sébastien, Rivest, Serge, Radzioch, Danuta, Olivier, Martin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.11.2001
• Subjects: Animals; Cell Line; I-kappa B Kinase; Inflammation; Intracellular Signaling Peptides and Proteins; Leishmania; Leishmania major; Leishmaniasis, Cutaneous - etiology; Leishmaniasis, Cutaneous - immunology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - physiology; Motheaten mice; Neutrophils - physiology; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide - physiology; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - physiology; Protein-Serine-Threonine Kinases - genetics; RNA, Messenger - analysis; SHP-1 protein; SHP‐1
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200111)31:11<3185::AID-IMMU3185>3.0.CO;2-J

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.