title: Bone marrow-imprinted gut-homing of plasmacytoid dendritic cells (pDCs) in acute simian immunodeficiency virus infection results in massive accumulation of hyperfunctional CD4+ pDCs in the mucosae.
abstract: Plasmacytoid dendritic cells (pDCs), a primary source of interferon α (IFN-α), provide a first line of innate immune defense against human immunodeficiency virus infection. However, their kinetics and functions during acute infection are poorly understood. In mucosal tissues of normal rhesus macaques, we found CD4(+) pDCs to be the subset responsible for most IFN-α and tumor necrosis factor α (TNF-α) production in response to Toll-like receptor (TLR) 7/8 stimulation, compared with relatively anergic CD4(-) pDCs. During acute simian immunodeficiency virus (SIV) infection, gut homing was imprinted on pDCs in the bone marrow, resulting in a decline in pDCs from circulation and secondary lymphoid tissues. Although the accumulated pDCs in the gut mucosae had robust cytokine responses to TLR7/8 stimulation in vitro, pDC gut migration occurred after infection and detection of SIV in plasma. Our data suggest that innate pDC responses do not control initial SIV seeding and dissemination but instead may contribute to ongoing immune activation in the gut.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston.
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: Tristan I
authors.initials: TI
authors.lastname: Evans
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gillis
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: Michelle
authors.initials: M
authors.lastname: Connole
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D008253:Macaca mulatta; D009928:Organ Specificity / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: SIV pathogenesis; mucosal immunology; plasmacytoid dendritic cell