The hitchhiker's guide to parasite dissemination

Cell Microbiol. 2019 Nov;21(11):e13070. doi: 10.1111/cmi.13070. Epub 2019 Jul 8.

Abstract

Toxoplasma gondii (T. gondii) is a parasitic protist that can infect nearly all nucleated cell types and tissues of warm-blooded vertebrate hosts. T. gondii utilises a unique form of gliding motility to cross cellular barriers, enter tissues, and penetrate host cells, thus enhancing spread within an infected host. However, T. gondii also disseminates by hijacking the migratory abilities of infected leukocytes. Traditionally, this process has been viewed as a route to cross biological barriers such as the blood-brain barrier. Here, we review recent findings that challenge this view by showing that infection of monocytes downregulates the program of transendothelial migration. Instead, infection by T. gondii enhances Rho-dependent interstitial migration of monocytes and macrophages, which enhances dissemination within tissues. Collectively, the available evidence indicates that T. gondii parasites use multiple means to disseminate within the host, including enhanced motility in tissues and translocation across biological barriers.

Keywords: actin-based motility; central nervous system infection; microbial-cell interaction; pathogen dissemination; protein kinase; transendothelial migration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / parasitology
  • Cell Movement
  • Central Nervous System Infections / immunology
  • Central Nervous System Infections / parasitology*
  • Host-Pathogen Interactions
  • Humans
  • Integrins / metabolism
  • Leukocytes / metabolism
  • Leukocytes / parasitology*
  • Macrophages / parasitology*
  • Monocytes / parasitology*
  • Toxoplasma / genetics
  • Toxoplasma / metabolism
  • Toxoplasma / pathogenicity*
  • Toxoplasmosis / immunology
  • Toxoplasmosis / metabolism
  • Toxoplasmosis / parasitology*
  • Toxoplasmosis / pathology
  • Transendothelial and Transepithelial Migration

Substances

  • Integrins