The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.

Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a crucial role in the first phase of host defense against infections and tumors. Listeria monocytogenes (Lm) is an intracellular pathogen that colonizes the cytosol of eukaryotic cells. Recen...

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Autores principales: Francesca Pontiroli, Olivier Dussurget, Ivan Zanoni, Matteo Urbano, Ottavio Beretta, Francesca Granucci, Paola Ricciardi-Castagnoli, Pascale Cossart, Maria Foti
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spelling oai:doaj.org-article:ded0381a402d4de991896ede3fa97fde2021-11-18T07:08:21ZThe timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.1932-620310.1371/journal.pone.0043455https://doaj.org/article/ded0381a402d4de991896ede3fa97fde2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22912878/?tool=EBIhttps://doaj.org/toc/1932-6203Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a crucial role in the first phase of host defense against infections and tumors. Listeria monocytogenes (Lm) is an intracellular pathogen that colonizes the cytosol of eukaryotic cells. Recent findings have shown Lm specifically in splenic CD8a(+) DCs shortly after intravenous infection. We examined gene expression profiles of mouse DCs exposed to Lm to elucidate the molecular mechanisms underlying DCs interaction with Lm. Using a functional genomics approach, we found that Lm infection induced a cluster of late response genes including type I IFNs and interferon responsive genes (IRGs) in DCs. Type I INFs were produced at the maximal level only at 24 h post infection indicating that the regulation of IFNs in the context of Lm infection is delayed compared to the rapid response observed with viral pathogens. We showed that during Lm infection, IFNγ production and cytotoxic activity were severely impaired in NK cells compared to E. coli infection. These defects were restored by providing an exogenous source of IFNβ during the initial phase of bacterial challenge. Moreover, when treated with IFNβ during early infection, NK cells were able to reduce bacterial titer in the spleen and significantly improve survival of infected mice. These findings show that the timing of IFNβ production is fundamental to the efficient control of the bacterium during the early innate phase of Lm infection.Francesca PontiroliOlivier DussurgetIvan ZanoniMatteo UrbanoOttavio BerettaFrancesca GranucciPaola Ricciardi-CastagnoliPascale CossartMaria FotiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e43455 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Francesca Pontiroli
Olivier Dussurget
Ivan Zanoni
Matteo Urbano
Ottavio Beretta
Francesca Granucci
Paola Ricciardi-Castagnoli
Pascale Cossart
Maria Foti
The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
description Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a crucial role in the first phase of host defense against infections and tumors. Listeria monocytogenes (Lm) is an intracellular pathogen that colonizes the cytosol of eukaryotic cells. Recent findings have shown Lm specifically in splenic CD8a(+) DCs shortly after intravenous infection. We examined gene expression profiles of mouse DCs exposed to Lm to elucidate the molecular mechanisms underlying DCs interaction with Lm. Using a functional genomics approach, we found that Lm infection induced a cluster of late response genes including type I IFNs and interferon responsive genes (IRGs) in DCs. Type I INFs were produced at the maximal level only at 24 h post infection indicating that the regulation of IFNs in the context of Lm infection is delayed compared to the rapid response observed with viral pathogens. We showed that during Lm infection, IFNγ production and cytotoxic activity were severely impaired in NK cells compared to E. coli infection. These defects were restored by providing an exogenous source of IFNβ during the initial phase of bacterial challenge. Moreover, when treated with IFNβ during early infection, NK cells were able to reduce bacterial titer in the spleen and significantly improve survival of infected mice. These findings show that the timing of IFNβ production is fundamental to the efficient control of the bacterium during the early innate phase of Lm infection.
format article
author Francesca Pontiroli
Olivier Dussurget
Ivan Zanoni
Matteo Urbano
Ottavio Beretta
Francesca Granucci
Paola Ricciardi-Castagnoli
Pascale Cossart
Maria Foti
author_facet Francesca Pontiroli
Olivier Dussurget
Ivan Zanoni
Matteo Urbano
Ottavio Beretta
Francesca Granucci
Paola Ricciardi-Castagnoli
Pascale Cossart
Maria Foti
author_sort Francesca Pontiroli
title The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
title_short The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
title_full The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
title_fullStr The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
title_full_unstemmed The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
title_sort timing of ifnβ production affects early innate responses to listeria monocytogenes and determines the overall outcome of lethal infection.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/ded0381a402d4de991896ede3fa97fde
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