| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* AIDS Research Center, National Institute of Infectious Diseases, Toyama, Shinjyuku-ku, Tokyo, Japan;
Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan;
Department of Pathology, New York University School of Medicine, New York, NY 10016;
Department of General Medicine, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan;
¶ Department of Pathology, Graduate School of Medicine, Yokohama City University, Fukuura, Kanazawa-ku, Kanagawa, Japan;
|| Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Uehara, Okinawa, Japan; and
# Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, Japan
Follicular dendritic cells (FDCs) are located in the lymphoid follicles of secondary lymphoid tissues and play a pivotal role in the selection of memory B lymphocytes within the germinal center, a major site for HIV-1 infection. Germinal centers are composed of highly activated B cells, macrophages, CD4+T cells, and FDCs. However, the physiological role of FDCs in HIV-1 replication remains largely unknown. We demonstrate in our current study that FDCs can efficiently activate HIV-1 replication in latently infected monocytic cells via an intercellular communication network mediated by the P-selectin/P-selectin glycoprotein ligand 1 (PSGL-1) interaction. Upon coculture with FDCs, HIV-1 replication was significantly induced in infected monocytic cell lines, primary monocytes, or macrophages. These cocultures were found to synergistically induce the expression of P-selectin in FDCs via NF-
B activation and its cognate receptor PSGL-1 in HIV-1-infected cells. Consistent with this observation, we find that this response is significantly blocked by antagonistic Abs against PSGL-1 and almost completely inhibited by PSGL-1 small interfering RNA. Moreover, a selective inhibitor for Syk, which is a downstream effector of PSGL-1, blocked HIV-1 replication in our cultures. We have thus elucidated a novel regulatory mechanism in which FDCs are a potent positive bystander that facilitates HIV-1 replication in adjacent infected monocytic cells via a juxtacrine signaling mechanism.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants from the Japanese Ministries of Education, Culture, Sports, Science and Technology (20390136, 13226027, 14406009, and 1941075) Health, Labour and Welfare (H18-005) and Human Health Science (H19-001) to N.Y. and A.R.
2 Address correspondence and reprint requests to Dr. Akihide Ryo and Dr. Naoki Yamamoto, AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjyuku-ku, Tokyo 162-8640, Japan. E-mail addresses: aryo{at}nih.go.jp and nyama{at}nih.go.jp
3 Abbreviations used in this paper: GC, germinal center; FDC, follicular dendritic cell; DC, dendritic cell; PSGL-1, P-selectin glycoprotein ligand 1; Syk, spleen tyrosine kinase; LTR, long terminal repeat; MOI, multiplicity of infection; siRNA, small interfering RNA.
4 The online version of this article contains supplemental material.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
