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Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection
Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence fro...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920340/ https://www.ncbi.nlm.nih.gov/pubmed/33647028 http://dx.doi.org/10.1371/journal.pone.0247125 |
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author | Mohamed, Hager Clemen, Ramona Freund, Eric Lackmann, Jan-Wilm Wende, Kristian Connors, Jennifer Haddad, Elias K. Dampier, Will Wigdahl, Brian Miller, Vandana Bekeschus, Sander Krebs, Fred C. |
author_facet | Mohamed, Hager Clemen, Ramona Freund, Eric Lackmann, Jan-Wilm Wende, Kristian Connors, Jennifer Haddad, Elias K. Dampier, Will Wigdahl, Brian Miller, Vandana Bekeschus, Sander Krebs, Fred C. |
author_sort | Mohamed, Hager |
collection | PubMed |
description | Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH. |
format | Online Article Text |
id | pubmed-7920340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79203402021-03-09 Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection Mohamed, Hager Clemen, Ramona Freund, Eric Lackmann, Jan-Wilm Wende, Kristian Connors, Jennifer Haddad, Elias K. Dampier, Will Wigdahl, Brian Miller, Vandana Bekeschus, Sander Krebs, Fred C. PLoS One Research Article Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH. Public Library of Science 2021-03-01 /pmc/articles/PMC7920340/ /pubmed/33647028 http://dx.doi.org/10.1371/journal.pone.0247125 Text en © 2021 Mohamed et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Mohamed, Hager Clemen, Ramona Freund, Eric Lackmann, Jan-Wilm Wende, Kristian Connors, Jennifer Haddad, Elias K. Dampier, Will Wigdahl, Brian Miller, Vandana Bekeschus, Sander Krebs, Fred C. Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection |
title | Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection |
title_full | Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection |
title_fullStr | Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection |
title_full_unstemmed | Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection |
title_short | Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection |
title_sort | non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent hiv-1 infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920340/ https://www.ncbi.nlm.nih.gov/pubmed/33647028 http://dx.doi.org/10.1371/journal.pone.0247125 |
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