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

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.

journal_name

Microb Pathog

journal_title

Microbial pathogenesis

authors

Lin HH,Chen HL,Janapatla RP,Chen CL,Chiu CH

doi

10.1016/j.micpath.2020.104222

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

104222

eissn

0882-4010

issn

1096-1208

pii

S0882-4010(20)30509-X

journal_volume

146

pub_type

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