An integrin/MFG-E8 shuttle loads HIV-1 viral-like particles onto follicular dendritic cells in mouse lymph node

Abstract

During human immunodeficiency virus-1 (HIV-1) infection lymphoid organ follicular dendritic cells (FDCs) serve as a reservoir for infectious virus and an obstacle to curative therapies. Here, we identify a subset of lymphoid organ sinus lining macrophage (SMs) that provide a cell-cell contact portal, which facilitates the uptake of HIV-1 viral-like particles (VLPs) by FDCs and B cells in mouse lymph node. Central for portal function is the bridging glycoprotein MFG-E8. Using a phosphatidylserine binding domain and an RGD motif, MFG-E8 helps target HIV-1 VLPs to αv integrin bearing SMs. Lack of MFG-E8 or integrin blockade severely limits HIV-1 VLP spread onto FDC networks. Direct SM-FDC virion transfer also depends upon short-lived FDC network abutment, likely triggered by SCSM antigen uptake. This provides a mechanism for rapid FDC loading broadening the opportunity for rare, antigen reactive follicular B cells to acquire antigen, and a means for HIV virions to accumulate on the FDC network.

LFA1 and ICAM1 are critical for fusion and spread of murine leukemia virus in vivo

“…Although in vitro co-cultures with peritoneal-cavity-derived macrophages indicate that ICAM2 does not contribute to trans-infection of MLV, an alternative mechanism might compensate for the lack of ICAM1 in vivo. Lymph or serum proteins containing integrinbinding motifs might recognize MLV particles and function as bridging factors to mediate cell-cell contacts for trans-infection in vivo, as recently described for the glycoprotein MFG-E8 during retrovirus infection (Park and Kehrl, 2019).…”

Unrestrained Gαi2 Signaling Disrupts Neutrophil Trafficking, Aging, and Clearance

“…Immunohistochemistry was performed as previously described ( 22 ). For imaging neutrophil recruitments from the BM, mice were injected i.v.…”

An optimized confocal intravital microscopy protocol for long-term live imaging of murine F-actin organization during naïve lymphocyte migration

“…Slight changes such as adjusting or repositioning the skin flap can help. Use the appropriate software such as Imaris to create 4D reconstructions from the acquired raw data file ( Yan et al., 2019 , Park and Kehrl, 2019 ). …”

“…Use the appropriate software such as Imaris to create 4D reconstructions from the acquired raw data file ( Yan et al., 2019 , Park and Kehrl, 2019 ).…”