Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling
The toll-like receptor (TLR) family comprises both cell-surface and intracellular receptors that recognize different types of pathogen-associated molecular patterns (PAMPs) leading to the production of pro-inflammatory cytokines and subsequent development of adaptive immunity. TLR2 is a cell-surface receptor initially thought to act as a bacterial sentinel but also shown to recognize a number of viral glycoproteins. In this study, we sought to characterize the role of TLR2 in the activation of the immune response by peste des petits ruminants virus (PPRV), a morbillivirus of the Paramixoviridae family that causes an acute, highly contagious disease in goats and sheep. Using human embryonic kidney (HEK) 293 cells stably expressing human (h)TLR2 but lacking any other TLR, we found that PPRV induces IL-8 production in a dose-dependent manner. That activation is only observed in cells expressing hTLR2 and is greatly reduced when the receptor is blocked by pretreatment with specific antibody. We identified hemagglutinin (H) as the viral protein responsible of TLR2 activation by performing the same assays with purified recombinant mammalian-expressed H protein. Exogenous addition of recombinant H protein to cell culture induces high levels of interleukin (IL)-8 only in TLR2-expressing cells. Moreover, H engagement on TLR2 in the monocytic cell line THP-1 activates extracellular-signal-regulated kinase (ERK) signaling. Stimulation of primary ovine dendritic cells with either inactivated PPRV or purified recombinant H protein results in transcription of pro-inflammatory cytokines and the secretion of the Th1-polarizing cytokine IL-12. The role of these host immune mechanisms in the control of PPR is discussed.
Main Authors: | , , , , , , , |
---|---|
Format: | artículo biblioteca |
Language: | English |
Published: |
Taylor & Francis
2021-01-01
|
Subjects: | TLR2, Morbillivirus, Hemagglutinin, Interleukin 8, Dendritic cells, Monocyte, Macrophage, ERK, |
Online Access: | http://hdl.handle.net/20.500.12792/6133 http://hdl.handle.net/10261/289565 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
dig-inia-es-10261-289565 |
---|---|
record_format |
koha |
spelling |
dig-inia-es-10261-2895652023-02-16T20:07:41Z Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling Rojas, Jose M Pascual, Elena Wattegedera, Sean R. Avia, Miguel Santiago, Cesar Martin, Veronica Entrican, Gary Sevilla, Noemi TLR2 Morbillivirus Hemagglutinin Interleukin 8 Dendritic cells Monocyte Macrophage ERK The toll-like receptor (TLR) family comprises both cell-surface and intracellular receptors that recognize different types of pathogen-associated molecular patterns (PAMPs) leading to the production of pro-inflammatory cytokines and subsequent development of adaptive immunity. TLR2 is a cell-surface receptor initially thought to act as a bacterial sentinel but also shown to recognize a number of viral glycoproteins. In this study, we sought to characterize the role of TLR2 in the activation of the immune response by peste des petits ruminants virus (PPRV), a morbillivirus of the Paramixoviridae family that causes an acute, highly contagious disease in goats and sheep. Using human embryonic kidney (HEK) 293 cells stably expressing human (h)TLR2 but lacking any other TLR, we found that PPRV induces IL-8 production in a dose-dependent manner. That activation is only observed in cells expressing hTLR2 and is greatly reduced when the receptor is blocked by pretreatment with specific antibody. We identified hemagglutinin (H) as the viral protein responsible of TLR2 activation by performing the same assays with purified recombinant mammalian-expressed H protein. Exogenous addition of recombinant H protein to cell culture induces high levels of interleukin (IL)-8 only in TLR2-expressing cells. Moreover, H engagement on TLR2 in the monocytic cell line THP-1 activates extracellular-signal-regulated kinase (ERK) signaling. Stimulation of primary ovine dendritic cells with either inactivated PPRV or purified recombinant H protein results in transcription of pro-inflammatory cytokines and the secretion of the Th1-polarizing cytokine IL-12. The role of these host immune mechanisms in the control of PPR is discussed. 2023-02-16T12:21:23Z 2023-02-16T12:21:23Z 2021-01-01 artículo Virulence 12:(1): 690-703 (2021) 2150-5594 http://hdl.handle.net/20.500.12792/6133 http://hdl.handle.net/10261/289565 10.1080/21505594.2021.1882246 2150-5608 33522421 en open Taylor & Francis |
institution |
INIA ES |
collection |
DSpace |
country |
España |
countrycode |
ES |
component |
Bibliográfico |
access |
En linea |
databasecode |
dig-inia-es |
tag |
biblioteca |
region |
Europa del Sur |
libraryname |
Biblioteca del INIA España |
language |
English |
topic |
TLR2 Morbillivirus Hemagglutinin Interleukin 8 Dendritic cells Monocyte Macrophage ERK TLR2 Morbillivirus Hemagglutinin Interleukin 8 Dendritic cells Monocyte Macrophage ERK |
spellingShingle |
TLR2 Morbillivirus Hemagglutinin Interleukin 8 Dendritic cells Monocyte Macrophage ERK TLR2 Morbillivirus Hemagglutinin Interleukin 8 Dendritic cells Monocyte Macrophage ERK Rojas, Jose M Pascual, Elena Wattegedera, Sean R. Avia, Miguel Santiago, Cesar Martin, Veronica Entrican, Gary Sevilla, Noemi Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling |
description |
The toll-like receptor (TLR) family comprises both cell-surface and intracellular receptors that
recognize different types of pathogen-associated molecular patterns (PAMPs) leading to the
production of pro-inflammatory cytokines and subsequent development of adaptive immunity.
TLR2 is a cell-surface receptor initially thought to act as a bacterial sentinel but also shown to
recognize a number of viral glycoproteins. In this study, we sought to characterize the role of TLR2
in the activation of the immune response by peste des petits ruminants virus (PPRV),
a morbillivirus of the Paramixoviridae family that causes an acute, highly contagious disease in
goats and sheep. Using human embryonic kidney (HEK) 293 cells stably expressing human (h)TLR2
but lacking any other TLR, we found that PPRV induces IL-8 production in a dose-dependent
manner. That activation is only observed in cells expressing hTLR2 and is greatly reduced when
the receptor is blocked by pretreatment with specific antibody. We identified hemagglutinin (H)
as the viral protein responsible of TLR2 activation by performing the same assays with purified
recombinant mammalian-expressed H protein. Exogenous addition of recombinant H protein to
cell culture induces high levels of interleukin (IL)-8 only in TLR2-expressing cells. Moreover,
H engagement on TLR2 in the monocytic cell line THP-1 activates extracellular-signal-regulated
kinase (ERK) signaling. Stimulation of primary ovine dendritic cells with either inactivated PPRV or
purified recombinant H protein results in transcription of pro-inflammatory cytokines and the
secretion of the Th1-polarizing cytokine IL-12. The role of these host immune mechanisms in the
control of PPR is discussed. |
format |
artículo |
topic_facet |
TLR2 Morbillivirus Hemagglutinin Interleukin 8 Dendritic cells Monocyte Macrophage ERK |
author |
Rojas, Jose M Pascual, Elena Wattegedera, Sean R. Avia, Miguel Santiago, Cesar Martin, Veronica Entrican, Gary Sevilla, Noemi |
author_facet |
Rojas, Jose M Pascual, Elena Wattegedera, Sean R. Avia, Miguel Santiago, Cesar Martin, Veronica Entrican, Gary Sevilla, Noemi |
author_sort |
Rojas, Jose M |
title |
Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling |
title_short |
Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling |
title_full |
Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling |
title_fullStr |
Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling |
title_full_unstemmed |
Hemagglutinin protein of Peste des Petits Ruminants virus (PPRV) activates the innate immune response via Toll-like receptor 2 signaling |
title_sort |
hemagglutinin protein of peste des petits ruminants virus (pprv) activates the innate immune response via toll-like receptor 2 signaling |
publisher |
Taylor & Francis |
publishDate |
2021-01-01 |
url |
http://hdl.handle.net/20.500.12792/6133 http://hdl.handle.net/10261/289565 |
work_keys_str_mv |
AT rojasjosem hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling AT pascualelena hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling AT wattegederaseanr hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling AT aviamiguel hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling AT santiagocesar hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling AT martinveronica hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling AT entricangary hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling AT sevillanoemi hemagglutininproteinofpestedespetitsruminantsviruspprvactivatestheinnateimmuneresponseviatolllikereceptor2signaling |
_version_ |
1767602981820170240 |