Universität zu Köln

Mohamed, Hager, Clemen, Ramona ORCID: 0000-0003-3877-3554, Freund, Eric ORCID: 0000-0003-2950-0984, Lackmann, Jan-Wilm, Wende, Kristian, Connors, Jennifer ORCID: 0000-0001-9137-0717, Haddad, Elias K., Dampier, Will, Wigdahl, Brian, Miller, Vandana ORCID: 0000-0002-2323-2299, Bekeschus, Sander and Krebs, Fred C. (2021). Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection. PLoS One, 16 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma); 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mohamed, Hager UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, Ramona UNSPECIFIED orcid.org/0000-0003-3877-3554 UNSPECIFIED Freund, Eric UNSPECIFIED orcid.org/0000-0003-2950-0984 UNSPECIFIED Lackmann, Jan-Wilm UNSPECIFIED UNSPECIFIED UNSPECIFIED Wende, Kristian UNSPECIFIED UNSPECIFIED UNSPECIFIED Connors, Jennifer UNSPECIFIED orcid.org/0000-0001-9137-0717 UNSPECIFIED Haddad, Elias K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dampier, Will UNSPECIFIED UNSPECIFIED UNSPECIFIED Wigdahl, Brian UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Vandana UNSPECIFIED orcid.org/0000-0002-2323-2299 UNSPECIFIED Bekeschus, Sander UNSPECIFIED UNSPECIFIED UNSPECIFIED Krebs, Fred C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-576198
DOI:	10.1371/journal.pone.0247125
Journal or Publication Title:	PLoS One
Volume:	16
Number:	3
Date:	2021
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57619