Elizabeth R Wonderlich1, Simon M Barratt-Boyes. 1. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract
BACKGROUND: During progressive simian immunodeficiency virus (SIV) infection, the ability of innate mononuclear phagocytes to function when responding to the invading pathogen has yet to be determined. METHODS: We generated single-stranded RNA (ssRNA) oligonucleotides from the infecting strain of virus and utilized them to stimulate mononuclear phagocytes from blood and lymph nodes of naïve and SIVmac251-infected rhesus macaques. RESULTS: Soon after infection and continuing through to chronic disease, plasmacytoid dendritic cells (pDC), monocytes, and macrophages from SIV-infected macaques were less able to produce pro-inflammatory cytokines after exposure to virus-derived toll-like receptor (TLR) agonists. In contrast, myeloid dendritic cells (mDC) became hyper-responsive during acute and stable chronic infection. CONCLUSIONS: Plasmacytoid dendritic cells, monocytes, and macrophages may not instigate continued immune activation by recognizing the single-stranded RNA from SIV as they are left dysfunctional after infection. Conversely, mDC functionality may be beneficial as their hyper-responsiveness is related to slowed disease progression.
BACKGROUND: During progressive simian immunodeficiency virus (SIV) infection, the ability of innate mononuclear phagocytes to function when responding to the invading pathogen has yet to be determined. METHODS: We generated single-stranded RNA (ssRNA) oligonucleotides from the infecting strain of virus and utilized them to stimulate mononuclear phagocytes from blood and lymph nodes of naïve and SIVmac251-infected rhesus macaques. RESULTS: Soon after infection and continuing through to chronic disease, plasmacytoid dendritic cells (pDC), monocytes, and macrophages from SIV-infected macaques were less able to produce pro-inflammatory cytokines after exposure to virus-derived toll-like receptor (TLR) agonists. In contrast, myeloid dendritic cells (mDC) became hyper-responsive during acute and stable chronic infection. CONCLUSIONS: Plasmacytoid dendritic cells, monocytes, and macrophages may not instigate continued immune activation by recognizing the single-stranded RNA from SIV as they are left dysfunctional after infection. Conversely, mDC functionality may be beneficial as their hyper-responsiveness is related to slowed disease progression.
Authors: J Judy Chang; Aurore Lacas; Robert J Lindsay; Erin H Doyle; Karen L Axten; Florencia Pereyra; Eric S Rosenberg; Bruce D Walker; Todd M Allen; Marcus Altfeld Journal: AIDS Date: 2012-03-13 Impact factor: 4.177
Authors: S Feldman; D Stein; S Amrute; T Denny; Z Garcia; P Kloser; Y Sun; N Megjugorac; P Fitzgerald-Bocarsly Journal: Clin Immunol Date: 2001-11 Impact factor: 3.969
Authors: G J Jones; C Watera; S Patterson; A Rutebemberwa; P Kaleebu; J A Whitworth; F M Gotch; J W Gilmour Journal: AIDS Date: 2001-09-07 Impact factor: 4.177
Authors: Michelle A Barron; Naomi Blyveis; Brent E Palmer; Samantha MaWhinney; Cara C Wilson Journal: J Infect Dis Date: 2002-12-13 Impact factor: 5.226