Follicular dendritic cells activate HIV-1 replication in monocytes/macrophages through a juxtacrine mechanism mediated by P-selectin glycoprotein ligand 1.
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-kappaB 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.
Ohba
Kenji
K
AIDS Research Center, National Institute of Infectious Diseases, Toyama, Shinjyuku-ku, Tokyo, Japan.
Ryo
Akihide
A
Dewan
Md Zahidunnabi
MZ
Nishi
Mayuko
M
Naito
Toshio
T
Qi
Xiaohua
X
Inagaki
Yoshio
Y
Nagashima
Yoji
Y
Tanaka
Yuetsu
Y
Okamoto
Takashi
T
Terashima
Kazuo
K
Yamamoto
Naoki
N
D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D019007:P-Selectin / Q000378:metabolism* / Q000502:physiology; D014066:Palatine Tonsil; D015398:Signal Transduction / Q000276:immunology; D014775:Virus Activation / Q000276:immunology; D017735:Virus Latency / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein