Exploitation of host cell signaling machinery: Activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis

D. Nandan, Keith L Knutson, R. Lo, N. E. Reiner

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Intracellular pathogens, particularly those that target host mononuclear phagocytes, have evolved strategies to either evade or inhibit cellular mechanisms of host defense. Mycobacterium tuberculosis and Leishmania donovani exemplify a diverse group of microorganisms that have developed the ability to invade and replicate within host macrophages, leading to disease expression. Recent studies have suggested that the pathogenesis of intracellular infection may involve interference with host cell signaling. Drawing upon examples from in vitro models that focused on M. tuberculosis and L. donovani, we review evidence that activation of host cell phosphotyrosine phosphatases may contribute to pathogenesis. A leading candidate appears to be the Src homology 2 domain containing phosphotyrosine phosphatase SHP-1, the activation of which may contribute to the development of infection and disease progression.

Original languageEnglish (US)
Pages (from-to)464-470
Number of pages7
JournalJournal of Leukocyte Biology
Volume67
Issue number4
StatePublished - 2000
Externally publishedYes

Fingerprint

Leishmania donovani
Protein Tyrosine Phosphatases
Macrophage Activation
Mycobacterium tuberculosis
SH2 Domain-Containing Protein Tyrosine Phosphatases
Phagocytes
Infection
Disease Progression
Macrophages
In Vitro Techniques

Keywords

  • Leishmania donovani
  • Mycobacterium tuberculosis
  • SHP-1
  • Src

ASJC Scopus subject areas

  • Cell Biology

Cite this

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AU - Reiner, N. E.

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AB - Intracellular pathogens, particularly those that target host mononuclear phagocytes, have evolved strategies to either evade or inhibit cellular mechanisms of host defense. Mycobacterium tuberculosis and Leishmania donovani exemplify a diverse group of microorganisms that have developed the ability to invade and replicate within host macrophages, leading to disease expression. Recent studies have suggested that the pathogenesis of intracellular infection may involve interference with host cell signaling. Drawing upon examples from in vitro models that focused on M. tuberculosis and L. donovani, we review evidence that activation of host cell phosphotyrosine phosphatases may contribute to pathogenesis. A leading candidate appears to be the Src homology 2 domain containing phosphotyrosine phosphatase SHP-1, the activation of which may contribute to the development of infection and disease progression.

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