The late endosomal adaptor p14 is a macrophage host-defense factor against Salmonella infection

J Cell Sci. 2012 Jun 1;125(Pt 11):2698-708. doi: 10.1242/jcs.100073. Epub 2012 Mar 16.

Abstract

The outcome of an infection depends on the balance between host resistance and bacterial virulence. Here, we show that the late endosomal adaptor p14 (also known as LAMTOR2) is one of the components for cellular host defense against the intracellular pathogen Salmonella enterica serovar Typhimurium. During Salmonella infection, the complex of p14 and MP1 is required for the accurately timed transport of Salmonella through the endolysosomal system. Loss of p14 opens a time window that allows Salmonella to populate a replication niche, in which early and late antimicrobial effector systems, comprising NADPH phagocytic oxidase and inducible nitric oxide synthase, respectively, are inappropriately activated. Thus, p14 supports the accurate transport of Salmonella through the endolysosomal system, thereby limiting bacterial replication in both, professional phagocytes and in non-phagocytic cells in vitro, and helps mice to successfully battle Salmonella infection in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Compartmentation
  • Disease Susceptibility
  • Endosomes / enzymology
  • Endosomes / ultrastructure
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Host-Pathogen Interactions / immunology*
  • Lysosomal Membrane Proteins / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Macrophages / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • NADPH Oxidases / metabolism
  • Phagocytosis
  • Protein Transport
  • Proteins / metabolism*
  • Salmonella Infections, Animal / immunology*
  • Salmonella Infections, Animal / microbiology*
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / physiology*
  • Vacuoles / metabolism
  • Vacuoles / microbiology
  • Vacuoles / ultrastructure

Substances

  • Adaptor Proteins, Signal Transducing
  • LAMTOR2 protein, mouse
  • Lamp1 protein, mouse
  • Lysosomal Membrane Proteins
  • Proteins
  • NADPH Oxidases
  • Extracellular Signal-Regulated MAP Kinases