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Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production
In humans and non-human primates, wild type (WT) measles virus (MeV) replicates extensively in lymphoid tissue and induces an innate response characteristic of NF-κB and inflammasome activation without type I interferon. In contrast, the live attenuated MeV vaccine (LAMV) replicates poorly in lympho...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961283/ https://www.ncbi.nlm.nih.gov/pubmed/36851476 http://dx.doi.org/10.3390/v15020260 |
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author | Suwanmanee, San Ghimire, Shristi Edwards, Jerome Griffin, Diane E. |
author_facet | Suwanmanee, San Ghimire, Shristi Edwards, Jerome Griffin, Diane E. |
author_sort | Suwanmanee, San |
collection | PubMed |
description | In humans and non-human primates, wild type (WT) measles virus (MeV) replicates extensively in lymphoid tissue and induces an innate response characteristic of NF-κB and inflammasome activation without type I interferon. In contrast, the live attenuated MeV vaccine (LAMV) replicates poorly in lymphoid tissue with little detectable in vivo cytokine production. To characterize the innate responses of macrophages to WT MeV and LAMV infection, we analyzed primary human monocyte-derived macrophages and phorbol myristic acid-matured monocytic THP-1 cells (M0) polarized to inflammatory (M1) and anti-inflammatory (M2) phenotypes 24 h after MeV infection. LAMV infected macrophages more efficiently than WT MeV but produced less virus than WT MeV-infected macrophages. Both strains induced production of NF-κB-responsive cytokines IL-6 and TNFα and inflammasome products IL-1β and IL-18 without evidence of pyroptosis. Analysis of THP-1 cells deficient in inflammasome sensors NOD-like receptor pyrin (NLRP)3, IFN-γ-inducible protein 16 (IFI16) or absent in melanoma (AIM)2; adaptor apoptosis-associated speck-like protein containing a CARD (ASC) or effector caspase 1 showed that IL-18 production was dependent on NLRP3, ASC, and caspase 1. However, M1 cells produced IL-1β in the absence of ASC or caspase 1 indicating alternate pathways for MeV-induced pro-IL-1β processing. Therefore, the innate response to in vitro infection of macrophages with both LAMV and WT MeV includes production of IL-6 and TNFα and activation of the NLRP3 inflammasome to release IL-1β and IL-18. LAMV attenuation impairs production of infectious virus but does not reduce ability to infect macrophages or innate responses to infection. |
format | Online Article Text |
id | pubmed-9961283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99612832023-02-26 Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production Suwanmanee, San Ghimire, Shristi Edwards, Jerome Griffin, Diane E. Viruses Article In humans and non-human primates, wild type (WT) measles virus (MeV) replicates extensively in lymphoid tissue and induces an innate response characteristic of NF-κB and inflammasome activation without type I interferon. In contrast, the live attenuated MeV vaccine (LAMV) replicates poorly in lymphoid tissue with little detectable in vivo cytokine production. To characterize the innate responses of macrophages to WT MeV and LAMV infection, we analyzed primary human monocyte-derived macrophages and phorbol myristic acid-matured monocytic THP-1 cells (M0) polarized to inflammatory (M1) and anti-inflammatory (M2) phenotypes 24 h after MeV infection. LAMV infected macrophages more efficiently than WT MeV but produced less virus than WT MeV-infected macrophages. Both strains induced production of NF-κB-responsive cytokines IL-6 and TNFα and inflammasome products IL-1β and IL-18 without evidence of pyroptosis. Analysis of THP-1 cells deficient in inflammasome sensors NOD-like receptor pyrin (NLRP)3, IFN-γ-inducible protein 16 (IFI16) or absent in melanoma (AIM)2; adaptor apoptosis-associated speck-like protein containing a CARD (ASC) or effector caspase 1 showed that IL-18 production was dependent on NLRP3, ASC, and caspase 1. However, M1 cells produced IL-1β in the absence of ASC or caspase 1 indicating alternate pathways for MeV-induced pro-IL-1β processing. Therefore, the innate response to in vitro infection of macrophages with both LAMV and WT MeV includes production of IL-6 and TNFα and activation of the NLRP3 inflammasome to release IL-1β and IL-18. LAMV attenuation impairs production of infectious virus but does not reduce ability to infect macrophages or innate responses to infection. MDPI 2023-01-17 /pmc/articles/PMC9961283/ /pubmed/36851476 http://dx.doi.org/10.3390/v15020260 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Suwanmanee, San Ghimire, Shristi Edwards, Jerome Griffin, Diane E. Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production |
title | Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production |
title_full | Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production |
title_fullStr | Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production |
title_full_unstemmed | Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production |
title_short | Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production |
title_sort | infection of pro- and anti-inflammatory macrophages by wild type and vaccine strains of measles virus: nlrp3 inflammasome activation independent of virus production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961283/ https://www.ncbi.nlm.nih.gov/pubmed/36851476 http://dx.doi.org/10.3390/v15020260 |
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