In Macrophages, Caspase-1 Activation by SopE and the Type III Secretion System-1 of S. Typhimurium Can Proceed in the Absence of Flagellin
| LEADER | caa a22 4500 | ||
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| 001 | 528787209 | ||
| 005 | 20190923032428.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924e20100830xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000022234 |2 doi |
| 024 | 7 | 0 | |a 10.1371/journal.pone.0012477 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/22234 | ||
| 245 | 0 | 0 | |a In Macrophages, Caspase-1 Activation by SopE and the Type III Secretion System-1 of S. Typhimurium Can Proceed in the Absence of Flagellin |h [Elektronische Daten] |c [Claudia Hoffmann, Marlies Galle, Sabrina Dilling, Rina Käppeli, Andreas J. Müller, Pascal Songhet, Rudi Beyaert, Wolf-Dietrich; id_orcid 0000-0002-9892-6420 Hardt] |
| 246 | 0 | |a PLoS ONE | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a The innate immune system is of vital importance for protection against infectious pathogens. Inflammasome mediated caspase-1 activation and subsequent release of pro-inflammatory cytokines like IL-1β and IL-18 is an important arm of the innate immune system. Salmonella enterica subspecies 1 serovar Typhimurium (S. Typhimurium, SL1344) is an enteropathogenic bacterium causing diarrheal diseases. Different reports have shown that in macrophages, S. Typhimurium may activate caspase-1 by at least three different types of stimuli: flagellin, the type III secretion system 1 (T1) and the T1 effector protein SopE. However, the relative importance and interdependence of the different factors in caspase-1 activation is still a matter of debate. Here, we have analyzed their relative contributions to caspase-1 activation in LPS-pretreated RAW264.7 macrophages. Using flagellar mutants (fliGHI, flgK) and centrifugation to mediate pathogen-host cell contact, we show that flagellins account for a small part of the caspase-1 activation in RAW264.7 cells. In addition, functional flagella are of key importance for motility and host cell attachment which is a prerequisite for mediating caspase-1 activation via these three stimuli. Using site directed mutants lacking several T1 effector proteins and flagellin expression, we found that SopE elicits caspase-1 activation even when flagellins are absent. In contrast, disruption of essential genes of the T1 protein injection system (invG, sipB) completely abolished caspase-1 activation. However, a robust level of caspase-1 activation is retained by the T1 system (or unidentified T1 effectors) in the absence of flagellin and SopE. T1-mediated inflammasome activation is in line with recent work by others and suggests that the T1 system itself may represent the basic caspase-1 activating stimulus in RAW264.7 macrophages which is further enhanced independently by SopE and/or flagellin. | |
| 540 | |a Creative Commons Attribution 3.0 Unported |u http://creativecommons.org/licenses/by/3.0 |2 ethresearch | ||
| 700 | 1 | |a Hoffmann |D Claudia |e joint author | |
| 700 | 1 | |a Galle |D Marlies |e joint author | |
| 700 | 1 | |a Dilling |D Sabrina |e joint author | |
| 700 | 1 | |a Käppeli |D Rina |e joint author | |
| 700 | 1 | |a Müller |D Andreas J. |e joint author | |
| 700 | 1 | |a Songhet |D Pascal |e joint author | |
| 700 | 1 | |a Beyaert |D Rudi |e joint author | |
| 700 | 1 | |a Hardt |D Wolf-Dietrich; id_orcid 0000-0002-9892-6420 |e joint author | |
| 773 | 0 | |t PLoS ONE |d Lawrence, KS, USA : PLoS |g 5 (8), p. e12477 |x 1932-6203 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/22234 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/22234 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Hoffmann |D Claudia |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Galle |D Marlies |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Dilling |D Sabrina |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Käppeli |D Rina |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Müller |D Andreas J. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Songhet |D Pascal |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Beyaert |D Rudi |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Hardt |D Wolf-Dietrich; id_orcid 0000-0002-9892-6420 |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t PLoS ONE |d Lawrence, KS, USA : PLoS |g 5 (8), p. e12477 |x 1932-6203 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||