Cargando…

Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines

HIV-1 replication is markedly upregulated in alveolar macrophages (AM) during pulmonary tuberculosis (TB). This is associated with loss of an inhibitory CCAAT enhancer binding protein β (C/EBPβ) transcription factor and activation of nuclear factor (NF)-κB. Since the cellular immune response in pulm...

Descripción completa

Detalles Bibliográficos
Autores principales: Hoshino, Yoshihiko, Nakata, Koh, Hoshino, Satomi, Honda, Yoshihiro, Tse, Doris B., Shioda, Tatsuo, Rom, William N., Weiden, Michael
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193627/
https://www.ncbi.nlm.nih.gov/pubmed/11854362
http://dx.doi.org/10.1084/jem.20011614
_version_ 1782147515544502272
author Hoshino, Yoshihiko
Nakata, Koh
Hoshino, Satomi
Honda, Yoshihiro
Tse, Doris B.
Shioda, Tatsuo
Rom, William N.
Weiden, Michael
author_facet Hoshino, Yoshihiko
Nakata, Koh
Hoshino, Satomi
Honda, Yoshihiro
Tse, Doris B.
Shioda, Tatsuo
Rom, William N.
Weiden, Michael
author_sort Hoshino, Yoshihiko
collection PubMed
description HIV-1 replication is markedly upregulated in alveolar macrophages (AM) during pulmonary tuberculosis (TB). This is associated with loss of an inhibitory CCAAT enhancer binding protein β (C/EBPβ) transcription factor and activation of nuclear factor (NF)-κB. Since the cellular immune response in pulmonary TB requires lymphocyte–macrophage interaction, a model system was developed in which lymphocytes were added to AM. Contact between lymphocytes and AM reduced inhibitory C/EBPβ, activated NF-κB, and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBPβ expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-κB was activated. Antibodies that cross-linked macrophage expressed B-7, and vascular cell adhesion molecule and CD40 were used to mimic lymphocyte contact. All three cross-linking antibodies were required to abolish inhibitory C/EBPβ expression. However, the HIV-1 LTR was not maximally stimulated and NF-κB was not activated. Maximal HIV-1–LTR stimulation required both lymphocyte-derived soluble factors, and cross-linking of macrophage expressed costimulatory molecules. High level HIV-1–LTR stimulation was also achieved when IL-1β, IL-6, and TNF-β were added to macrophages with cross-linked costimulatory molecules. Contact between activated lymphocytes and macrophages is necessary to down-regulate inhibitory C/EBPβ, thereby derepressing the HIV-1 LTR. Lymphocyte-derived cytokines activate NF-κB, further enhancing the HIV-1 LTR.
format Text
id pubmed-2193627
institution National Center for Biotechnology Information
language English
publishDate 2002
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21936272008-04-14 Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines Hoshino, Yoshihiko Nakata, Koh Hoshino, Satomi Honda, Yoshihiro Tse, Doris B. Shioda, Tatsuo Rom, William N. Weiden, Michael J Exp Med Original Article HIV-1 replication is markedly upregulated in alveolar macrophages (AM) during pulmonary tuberculosis (TB). This is associated with loss of an inhibitory CCAAT enhancer binding protein β (C/EBPβ) transcription factor and activation of nuclear factor (NF)-κB. Since the cellular immune response in pulmonary TB requires lymphocyte–macrophage interaction, a model system was developed in which lymphocytes were added to AM. Contact between lymphocytes and AM reduced inhibitory C/EBPβ, activated NF-κB, and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBPβ expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-κB was activated. Antibodies that cross-linked macrophage expressed B-7, and vascular cell adhesion molecule and CD40 were used to mimic lymphocyte contact. All three cross-linking antibodies were required to abolish inhibitory C/EBPβ expression. However, the HIV-1 LTR was not maximally stimulated and NF-κB was not activated. Maximal HIV-1–LTR stimulation required both lymphocyte-derived soluble factors, and cross-linking of macrophage expressed costimulatory molecules. High level HIV-1–LTR stimulation was also achieved when IL-1β, IL-6, and TNF-β were added to macrophages with cross-linked costimulatory molecules. Contact between activated lymphocytes and macrophages is necessary to down-regulate inhibitory C/EBPβ, thereby derepressing the HIV-1 LTR. Lymphocyte-derived cytokines activate NF-κB, further enhancing the HIV-1 LTR. The Rockefeller University Press 2002-02-18 /pmc/articles/PMC2193627/ /pubmed/11854362 http://dx.doi.org/10.1084/jem.20011614 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Hoshino, Yoshihiko
Nakata, Koh
Hoshino, Satomi
Honda, Yoshihiro
Tse, Doris B.
Shioda, Tatsuo
Rom, William N.
Weiden, Michael
Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines
title Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines
title_full Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines
title_fullStr Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines
title_full_unstemmed Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines
title_short Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines
title_sort maximal hiv-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193627/
https://www.ncbi.nlm.nih.gov/pubmed/11854362
http://dx.doi.org/10.1084/jem.20011614
work_keys_str_mv AT hoshinoyoshihiko maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines
AT nakatakoh maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines
AT hoshinosatomi maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines
AT hondayoshihiro maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines
AT tsedorisb maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines
AT shiodatatsuo maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines
AT romwilliamn maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines
AT weidenmichael maximalhiv1replicationinalveolarmacrophagesduringtuberculosisrequiresbothlymphocytecontactandcytokines