Characterization of the NLRP1 inflammasome response in bovine species
Inflammasomes act as sensors of infection or damage to initiate immune responses. While extensively studied in rodents, understanding of livestock inflammasomes is limited. The NLRP1 inflammasome sensor in rodents is activated by Toxoplasma gondii , Bacillus anthracis lethal toxin (LT), and potentia...
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Series: | Innate Immunity |
Online Access: | https://doi.org/10.1177/1753425919886649 |
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doaj-7b19d86c1cc34d338a1536ddf99408962020-11-25T04:10:49ZengSAGE PublishingInnate Immunity1753-42591753-42672020-05-012610.1177/1753425919886649Characterization of the NLRP1 inflammasome response in bovine speciesCatherine E VrentasPaola M BoggiattoSteven C OlsenStephen H LepplaMahtab MoayeriInflammasomes act as sensors of infection or damage to initiate immune responses. While extensively studied in rodents, understanding of livestock inflammasomes is limited. The NLRP1 inflammasome sensor in rodents is activated by Toxoplasma gondii , Bacillus anthracis lethal toxin (LT), and potentially other zoonotic pathogens. LT activates NLRP1 by N-terminal proteolysis, inducing macrophage pyroptosis and a pro-inflammatory cytokine response. In contrast, NLRP1 in macrophages from humans and certain rodent strains is resistant to LT cleavage, and pyroptosis is not induced. Evolution of NLRP1 sequences towards those leading to pyroptosis is of interest in understanding innate immune responses in different hosts. We characterized NLRP1 in cattle ( Bos taurus ) and American bison ( Bison bison ). Bovine NLRP1 is not cleaved by LT, and cattle and bison macrophages do not undergo toxin-induced pyroptosis. Additionally, we found a predicted Nlrp1 splicing isoform in cattle macrophages lacking the N-terminal domain. Resistance to LT in bovine and human NLRP1 correlates with evolutionary sequence similarity to rodents. Consistent with LT-resistant rodents, bovine macrophages undergo a slower non-pyroptotic death in the presence of LPS and LT. Overall, our findings support the model that NLRP1 activation by LT requires N-terminal cleavage, and provide novel information on mechanisms underlying immune response diversity.https://doi.org/10.1177/1753425919886649 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catherine E Vrentas Paola M Boggiatto Steven C Olsen Stephen H Leppla Mahtab Moayeri |
spellingShingle |
Catherine E Vrentas Paola M Boggiatto Steven C Olsen Stephen H Leppla Mahtab Moayeri Characterization of the NLRP1 inflammasome response in bovine species Innate Immunity |
author_facet |
Catherine E Vrentas Paola M Boggiatto Steven C Olsen Stephen H Leppla Mahtab Moayeri |
author_sort |
Catherine E Vrentas |
title |
Characterization of the NLRP1 inflammasome response in bovine species |
title_short |
Characterization of the NLRP1 inflammasome response in bovine species |
title_full |
Characterization of the NLRP1 inflammasome response in bovine species |
title_fullStr |
Characterization of the NLRP1 inflammasome response in bovine species |
title_full_unstemmed |
Characterization of the NLRP1 inflammasome response in bovine species |
title_sort |
characterization of the nlrp1 inflammasome response in bovine species |
publisher |
SAGE Publishing |
series |
Innate Immunity |
issn |
1753-4259 1753-4267 |
publishDate |
2020-05-01 |
description |
Inflammasomes act as sensors of infection or damage to initiate immune responses. While extensively studied in rodents, understanding of livestock inflammasomes is limited. The NLRP1 inflammasome sensor in rodents is activated by Toxoplasma gondii , Bacillus anthracis lethal toxin (LT), and potentially other zoonotic pathogens. LT activates NLRP1 by N-terminal proteolysis, inducing macrophage pyroptosis and a pro-inflammatory cytokine response. In contrast, NLRP1 in macrophages from humans and certain rodent strains is resistant to LT cleavage, and pyroptosis is not induced. Evolution of NLRP1 sequences towards those leading to pyroptosis is of interest in understanding innate immune responses in different hosts. We characterized NLRP1 in cattle ( Bos taurus ) and American bison ( Bison bison ). Bovine NLRP1 is not cleaved by LT, and cattle and bison macrophages do not undergo toxin-induced pyroptosis. Additionally, we found a predicted Nlrp1 splicing isoform in cattle macrophages lacking the N-terminal domain. Resistance to LT in bovine and human NLRP1 correlates with evolutionary sequence similarity to rodents. Consistent with LT-resistant rodents, bovine macrophages undergo a slower non-pyroptotic death in the presence of LPS and LT. Overall, our findings support the model that NLRP1 activation by LT requires N-terminal cleavage, and provide novel information on mechanisms underlying immune response diversity. |
url |
https://doi.org/10.1177/1753425919886649 |
work_keys_str_mv |
AT catherineevrentas characterizationofthenlrp1inflammasomeresponseinbovinespecies AT paolamboggiatto characterizationofthenlrp1inflammasomeresponseinbovinespecies AT stevencolsen characterizationofthenlrp1inflammasomeresponseinbovinespecies AT stephenhleppla characterizationofthenlrp1inflammasomeresponseinbovinespecies AT mahtabmoayeri characterizationofthenlrp1inflammasomeresponseinbovinespecies |
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