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.
Skip Nav Destination
Article navigation
18 February 2002
Article|
February 19 2002
Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines
Yoshihiko Hoshino,
Yoshihiko Hoshino
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Search for other works by this author on:
Koh Nakata,
Koh Nakata
3Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan
Search for other works by this author on:
Satomi Hoshino,
Satomi Hoshino
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Search for other works by this author on:
Yoshihiro Honda,
Yoshihiro Honda
4Department of Medicine, Sendai Kosei Hospital, Sendai 980-0873, Japan
Search for other works by this author on:
Doris B. Tse,
Doris B. Tse
2Division of Infectious Disease and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016
Search for other works by this author on:
Tatsuo Shioda,
Tatsuo Shioda
5Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Search for other works by this author on:
William N. Rom,
William N. Rom
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Search for other works by this author on:
Michael Weiden
Michael Weiden
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Search for other works by this author on:
Yoshihiko Hoshino
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Koh Nakata
3Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan
Satomi Hoshino
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Yoshihiro Honda
4Department of Medicine, Sendai Kosei Hospital, Sendai 980-0873, Japan
Doris B. Tse
2Division of Infectious Disease and Immunology, Department of Medicine, New York University School of Medicine, New York, NY 10016
Tatsuo Shioda
5Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
William N. Rom
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Michael Weiden
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016
Address correspondence to Michael Weiden, Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016. Phone: 212-263-7889; Fax: 212-263-8501; E-mail: [email protected]
*
Abbreviations used in this paper: AM, alveolar macrophages; BAL, bronchoalveolar lavage; CAT, chloramphenicol acetyltransferase; C/EBPβ, CCAAT enhancer binding protein β; EMSA, electrophoretic mobility shift assay; LTR, long terminal repeat; NF, nuclear factor; NRE, negative regulatory element; TB, tuberculosis; VCAM, vascular cell adhesion molecule; VLA, very late antigen.
Received:
September 20 2001
Revision Received:
December 13 2001
Accepted:
January 08 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (4): 495–505.
Article history
Received:
September 20 2001
Revision Received:
December 13 2001
Accepted:
January 08 2002
Citation
Yoshihiko Hoshino, Koh Nakata, Satomi Hoshino, Yoshihiro Honda, Doris B. Tse, Tatsuo Shioda, William N. Rom, Michael Weiden; Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines . J Exp Med 18 February 2002; 195 (4): 495–505. doi: https://doi.org/10.1084/jem.20011614
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement