Hyperexpression of type III secretion system of Salmonella Typhi linked to a higher cytotoxic effect to monocyte-derived macrophages by activating inflammasome

Hsin Hung Lin, Hsiu Ling Chen, Rajendra Prasad Janapatla, Chyi Liang Chen, Cheng Hsun Chiu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

4 Scopus citations

Abstract

Inflammasome activation is an important host response to infectious diseases, but the difference in inflammasome activation between typhoid fever and non-typhoidal Salmonella infection has been rarely studied. To determine whether inflammasome activation in macrophages after S. Typhi and S. Typhimurium infection is different, we measured pyroptosis, caspase-1 activation, and IL-1β secretion in monocyte-derived macrophages infected with S. Typhi or S. Typhimurium both in vitro and ex vivo. The role of Vi capsule and virulence genes in Salmonella pathogenicity island-1 (SPI-1), belonging to type III secretion system, was also examined. S. Typhi caused more pyroptosis, caspase-1 activation, and IL-1β production than S. Typhimurium did, predominantly within 2 h of infection, in the context of high number of infecting bacteria. Mutagenesis and complementation experiments confirmed that SPI-1 effectors but not Vi were associated with greater inflammasome activation. The expression levels of invA and hilA were significantly higher in S. Typhi than in S. Typhimurium at early log phase in SPI-1 environment. Thus, S. Typhi, relative to its non-typhoidal counterpart, S. Typhimurium, induces greater SPI-1-dependent inflammasome activation in monocyte-derived macrophages. This finding may explain why S. Typhi causes a hyperinflammatory state at bacteremic stage in typhoid fever.

Original languageEnglish
Article number104222
JournalMicrobial Pathogenesis
Volume146
DOIs
StatePublished - 09 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Inflammasome activation
  • Salmonella Typhi
  • Salmonella pathogenicity island-1
  • Type III secretion System

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