Open AccessFollicular Dendritic Cells Activate HIV-1 Replication in Monocytes/Macrophages through a Juxtacrine Mechanism Mediated by P-Selectin Glycoprotein Ligand 1
Author(s) -
Kenji Ohba,
Akihide Ryo,
M. Zahidunnabi Dewan,
Mayuko Nishi,
Toshio Naito,
Xiaohua Qi,
Yutaka Inagaki,
Yoji Nagashima,
Yuetsu Tanaka,
Takashi Okamoto,
Kazuo Terashima,
Naoki Yamamoto
Publication year - 2009
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.0900371
Subject(s) - microbiology and biotechnology , germinal center , follicular dendritic cells , biology , juxtacrine signalling , tetherin , viral replication , b cell , receptor , immunology , t cell , antigen presenting cell , immune system , virus , antibody , paracrine signalling , biochemistry
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.