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 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.
Competing Interests: JC is inventor of a patent related to Ecotin. The patent “Immunomodulating and immunostimulating polypeptides for drug-delivery” was filled on February 8, 2019 by the authors’ National Research Council (CONICET) and the University of San Martin (UNSAM) in the United States patent and trademark Office (US2021009371), the European patent office (PCT/IB2019/051026, EP3749364), the China National intellectual property administration (CN111936166), and the National Institute of Intellectual Property from Argentina (AR114683). The filing of the patent did not have any role in experimental design, data collection and analysis, decision to publish, or preparation of this manuscript. The authors have no financial conflicts of interest.
(Copyright: © 2023 Sabbione et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)