Induction of Krüppel-Like Factor 4 Mediates Polymorphonuclear Neutrophil Activation in Streptococcus pneumoniae Infection

Autor: Bhattacharyya, Aritra, Herta, Toni, Conrad, Claudia, Frey, Doris, García, Pedro, Suttorp, Norbert, Hippenstiel, Stefan, Zahlten, Janine
Přispěvatelé: German Research Foundation, Ministerio de Economía, Industria y Competitividad (España), Instituto de Salud Carlos III, Charité - Universitätsmedizin Berlin, Herta, Toni, Frey, Doris, García, Pedro, Suttorp, Norbert, Hippenstiel, Stefan, Zahlten, Janine, Herta, Toni [0000-0002-0401-1140], Frey, Doris [0000-0002-6536-3377], García, Pedro [0000-0001-6717-8717], Suttorp, Norbert [0000-0002-3958-1151], Hippenstiel, Stefan [0000-0002-5146-1064], Zahlten, Janine [0000-0002-3919-2113 ]
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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ISSN: 1664-302X
DOI: 10.3389/fmicb.2020.582070
Popis: 9 p.-3 fig.
The recruitment and activation of polymorphonuclear neutrophils (PMNs) are of central importance for the elimination of pathogens in bacterial infections. We investigated the Streptococcus pneumoniae-dependent induction of the transcription factor Krüppel-like factor (KLF) 4 in PMNs as a potential regulator of PMN activation. We found that KLF4 expression is induced in human blood-derived PMNs in a time- and dose-dependent manner by wild-type S. pneumoniae and capsule knockout mutants. Unencapsulated knockout mutants induced stronger KLF4 expression than encapsulated wild types. The presence of autolysin LytA-competent (thus viable) pneumococci and LytA-mediated bacterial autolysis were required for KLF4 induction in human and murine PMNs. LyzMcre-mediated knockdown of KLF4 in murine blood-derived PMNs revealed that KLF4 influences pneumococci killing and increases the release of the proinflammatory cytokines tumor necrosis factor α and keratinocyte chemoattractant and decreases the release of the anti-inflammatory cytokine interleukin-10. Thus, S. pneumoniae induces KLF4 expression in PMNs, which contributes to PMN activation in S. pneumoniae infection.
This work was supported by DFG SFB-TR84 grants to JZ, SH, and NS (projects C2, B1, and B6), Jürgen Manchot Stiftung to AB and TH and SAF2017-88664-R and CIBER de Enfermedades Respiratorias [an initiative of the Instituto de Salud Carlos III (ISCIII)] to PG. The publication was supported by the German Research Foundation (DFG) and the Open Access Publication Fund of Charité – Universitätsmedizin Berlin.
Databáze: OpenAIRE