Regulation of human neutrophil IL-1ß secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome.
PLoS Pathog
; 19(12): e1011877, 2023 Dec.
Article
in En
| MEDLINE
| ID: mdl-38127952
ABSTRACT
Shiga-toxin producing Escherichia coli (STEC) infections can cause from bloody diarrhea to Hemolytic Uremic Syndrome. The STEC intestinal infection triggers an inflammatory response that can facilitate the development of a systemic disease. We report here that neutrophils might contribute to this inflammatory response by secreting Interleukin 1 beta (IL-1ß). STEC stimulated neutrophils to release elevated levels of IL-1ß through a mechanism that involved the activation of caspase-1 driven by the NLRP3-inflammasome and neutrophil serine proteases (NSPs). Noteworthy, IL-1ß secretion was higher at lower multiplicities of infection. This secretory profile modulated by the bacterianeutrophil ratio, was the consequence of a regulatory mechanism that reduced IL-1ß secretion the higher were the levels of activation of both caspase-1 and NSPs, and the production of NADPH oxidase-dependent reactive oxygen species. Finally, we also found that inhibition of NSPs significantly reduced STEC-triggered IL-1ß secretion without modulating the ability of neutrophils to kill the bacteria, suggesting NSPs might represent pharmacological targets to be evaluated to limit the STEC-induced intestinal inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Escherichia coli O157
/
Escherichia coli Infections
/
Interleukin-1beta
/
Shiga-Toxigenic Escherichia coli
/
Hemolytic-Uremic Syndrome
Limits:
Humans
Language:
En
Journal:
PLoS Pathog
Year:
2023
Document type:
Article
Affiliation country:
Argentina