Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome.
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 in...
Main Authors: | , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2023-12-01
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Series: | PLoS Pathogens |
Online Access: | https://doi.org/10.1371/journal.ppat.1011877 |
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author | Florencia Sabbione Irene Angelica Keitelman Carolina Maiumi Shiromizu Alexia Vereertbrugghen Douglas Vera Aguilar Paolo Nahuel Rubatto Birri Manuela Pizzano María Victoria Ramos Federico Fuentes Lucas Saposnik Agostina Cernutto Juliana Cassataro Carolina Cristina Jancic Jeremías Gaston Galletti Marina Sandra Palermo Analía Silvina Trevani |
author_facet | Florencia Sabbione Irene Angelica Keitelman Carolina Maiumi Shiromizu Alexia Vereertbrugghen Douglas Vera Aguilar Paolo Nahuel Rubatto Birri Manuela Pizzano María Victoria Ramos Federico Fuentes Lucas Saposnik Agostina Cernutto Juliana Cassataro Carolina Cristina Jancic Jeremías Gaston Galletti Marina Sandra Palermo Analía Silvina Trevani |
author_sort | Florencia Sabbione |
collection | DOAJ |
description | 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-1β). STEC stimulated neutrophils to release elevated levels of IL-1β through a mechanism that involved the activation of caspase-1 driven by the NLRP3-inflammasome and neutrophil serine proteases (NSPs). Noteworthy, IL-1β secretion was higher at lower multiplicities of infection. This secretory profile modulated by the bacteria:neutrophil ratio, was the consequence of a regulatory mechanism that reduced IL-1β 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-1β 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. |
first_indexed | 2024-03-08T03:10:29Z |
format | Article |
id | doaj.art-13e6d641ecc14884bbe7d0e182742c43 |
institution | Directory Open Access Journal |
issn | 1553-7366 1553-7374 |
language | English |
last_indexed | 2024-03-08T03:10:29Z |
publishDate | 2023-12-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Pathogens |
spelling | doaj.art-13e6d641ecc14884bbe7d0e182742c432024-02-13T05:32:25ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-12-011912e101187710.1371/journal.ppat.1011877Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome.Florencia SabbioneIrene Angelica KeitelmanCarolina Maiumi ShiromizuAlexia VereertbrugghenDouglas Vera AguilarPaolo Nahuel Rubatto BirriManuela PizzanoMaría Victoria RamosFederico FuentesLucas SaposnikAgostina CernuttoJuliana CassataroCarolina Cristina JancicJeremías Gaston GallettiMarina Sandra PalermoAnalía Silvina TrevaniShiga-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-1β). STEC stimulated neutrophils to release elevated levels of IL-1β through a mechanism that involved the activation of caspase-1 driven by the NLRP3-inflammasome and neutrophil serine proteases (NSPs). Noteworthy, IL-1β secretion was higher at lower multiplicities of infection. This secretory profile modulated by the bacteria:neutrophil ratio, was the consequence of a regulatory mechanism that reduced IL-1β 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-1β 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.https://doi.org/10.1371/journal.ppat.1011877 |
spellingShingle | Florencia Sabbione Irene Angelica Keitelman Carolina Maiumi Shiromizu Alexia Vereertbrugghen Douglas Vera Aguilar Paolo Nahuel Rubatto Birri Manuela Pizzano María Victoria Ramos Federico Fuentes Lucas Saposnik Agostina Cernutto Juliana Cassataro Carolina Cristina Jancic Jeremías Gaston Galletti Marina Sandra Palermo Analía Silvina Trevani Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome. PLoS Pathogens |
title | Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome. |
title_full | Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome. |
title_fullStr | Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome. |
title_full_unstemmed | Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome. |
title_short | Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome. |
title_sort | regulation of human neutrophil il 1β secretion induced by escherichia coli o157 h7 responsible for hemolytic uremic syndrome |
url | https://doi.org/10.1371/journal.ppat.1011877 |
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