Virulence factors perforate the pathogen-containing vacuole to signal efferocytosis

Hirotaka Hiyoshi, Bevin C. English, Vladimir E. Diaz-Ochoa, Tamding Wangdi, Lillian F. Zhang, Miako Sakaguchi, Takeshi Haneda, Renée M. Tsolis, Andreas J. Bäumler

Research output: Contribution to journalArticlepeer-review

Abstract

Intracellular pathogens commonly reside within macrophages to find shelter from humoral defenses, but host cell death can expose them to the extracellular milieu. We find intracellular pathogens solve this dilemma by using virulence factors to generate a complement-dependent find-me signal that initiates uptake by a new phagocyte through efferocytosis. During macrophage death, Salmonella uses a type III secretion system to perforate the membrane of the pathogen-containing vacuole (PCV), thereby triggering complement deposition on bacteria entrapped in pore-induced intracellular traps (PITs). In turn, complement activation signals neutrophil efferocytosis, a process that shelters intracellular bacteria from the respiratory burst. Similarly, Brucella employs its type IV secretion system to perforate the PCV membrane, which induces complement deposition on bacteria entrapped in PITs. Collectively, this work identifies virulence factor-induced perforation of the PCV as a strategy of intracellular pathogens to generate a find-me signal for efferocytosis.

Original languageEnglish (US)
Pages (from-to)163-170.e6
JournalCell Host and Microbe
Volume30
Issue number2
DOIs
StatePublished - Feb 9 2022

Keywords

  • Brucella
  • complement
  • efferocytosis
  • macrophage
  • neutrophil
  • Salmonella

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Fingerprint

Dive into the research topics of 'Virulence factors perforate the pathogen-containing vacuole to signal efferocytosis'. Together they form a unique fingerprint.

Cite this