Derepression of Salmonella pathogenicity island 1 genes within macrophages leads to rapid apoptosis via caspase-1- and caspase-3-dependent pathways

Akiko Takaya, Akiko Suzuki, Yuji Kikuchi, Masahiro Eguchi, Emiko Isogai, Toshifumi Tomoyasu, Tomoko Yamamoto

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Salmonella enterica serovar Typhimurium has been reported to induce apoptosis in infected macrophages within 14 h from the time of infection by a caspase-1-dependent mechanism. Here, we demonstrate that depletion of Lon protease in serovar Typhimurium induces rapid and massive apoptosis in macrophages by a mechanism involving both caspases-1 and -3. This excessive induction of apoptosis was abrogated by disruption of invF, which is required for the expression of the Salmonella pathogenicity island 1 (SPI1) genes. Expression of hilA, a central regulator of SPI1 transcription, was repressed in the macrophages after phagocytosis, but this gene was continuously expressed when the ΔLon mutant grew within the macrophages, so the SPI1 proteins accumulated. Thus, the increase in macrophage apoptosis induced by the ΔLon mutant could result from continued expression of SPI1 genes under conditions where they are normally repressed. Once Salmonella has established a systemic infection, excess apoptosis of macrophages cells upon which the organism is reliant would be detrimental to the pathogen. Therefore, the Lon protease may be required to suppress apoptosis sufficiently to allow time for the bacterium to replicate, escape and invade new macrophages.

Original languageEnglish
Pages (from-to)79-90
Number of pages12
JournalCellular Microbiology
Volume7
Issue number1
DOIs
Publication statusPublished - 2005 Jan

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'Derepression of Salmonella pathogenicity island 1 genes within macrophages leads to rapid apoptosis via caspase-1- and caspase-3-dependent pathways'. Together they form a unique fingerprint.

Cite this