Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type 1 with Alpha Interferon Production and Maturation into Dendritic Cells

Yonezawa, Akihito; Morita, Rimpei; Takaori‐Kondo, Akifumi; Kadowaki, Norimitsu; Kitawaki, Toshio; Hori, Tomohide; Uchiyama, Takashi

doi:10.1128/jvi.77.6.3777-3784.2003

Cited by 102 publications

(107 citation statements)

References 39 publications

(41 reference statements)

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“…This hypothesis is corroborated by the results recently published by Yonezawa et al [39]. Indeed, although human DC that are generated in vitro do not mature after infection by HIV (this phenomenon might be actually due to some interference of HIV proteins with the DC maturation pathways [40]), plasmacytoid DC, which can be activated by stabilized RNA (B. Scheel, ongoing studies), mature in contact with infectious or heat-inactivated HIV.…”

Section: Discussionsupporting

confidence: 63%

Immunostimulating capacities of stabilized RNA molecules

Scheel

Braedel²,

Probst³

et al. 2004

Eur J Immunol

126

112

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Since direct injection of naked mRNA induces an immune response, we tested the capacity of RNA to signal danger. We show here that mRNA molecules that are protected from immediate degradation either through interaction with cationic proteins (trans protection) or through chemical modification of the phosphodiester backbone (phosphorothioate RNA; cis protection) act as sequence-independent danger signals on mouse DC. As opposed to CpG DNA, the cis-stabilized RNA is degraded in a few minutes, does not activate B cells and, in contrast to double-stranded RNA, requires MyD88 for activation of the DC. We postulate that phosphorothioate RNA, which mimics trans-stabilized RNA, is a new PAMP.

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Section: Discussionsupporting

confidence: 63%

Immunostimulating capacities of stabilized RNA molecules

Scheel

Braedel²,

Probst³

et al. 2004

Eur J Immunol

126

112

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“…Contrasting what we observed in the blood where there were more PDCs in PBMCs from SHIVinfected monkeys (17), the percentages of PDCs were comparable in LNCs from naive and SHIV-infected animals. HIV reportedly infects blood-derived PDCs, increasing cell viability (83,84), and this may be what we have observed in the blood but not LNs of the SHIV-infected animals. Whether this reflects inherent differences between PDCs in the blood and lymphoid tissues and/or differences in the distribution of DC subsets between blood and tissues needs to be elucidated.…”

Section: Discussionsupporting

confidence: 52%

Local and Systemic Effects of Intranodally Injected CpG-C Immunostimulatory-Oligodeoxyribonucleotides in Macaques

Teleshova

Kenney

Nest

et al. 2006

The Journal of Immunology

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Immunostimulatory CpG-C oligodeoxyribonucleotides (ISS-ODNs) represent a promising strategy to enhance vaccine efficacy. We have shown that the CpG-C ISS-ODN C274 stimulates macaque blood dendritic cells (DCs) and B cells and augments SIV-specific IFN-γ responses in vitro. To further explore the potential of C274 for future vaccine studies, we assessed the in vivo effects of locally administered C274 (in naive and healthy infected macaques). Costimulatory molecules were marginally increased on DCs and B cells within cells isolated from C274-injected lymph nodes (LNs). However, cells from C274-injected LNs exhibited heightened responsiveness to in vitro culture. This was particularly apparent at the level of CD80 (less so CD86) expression by CD123+ plasmacytoid DCs and was further boosted in the presence of additional C274 in vitro. Notably, cells from C274-injected LNs secreted significantly elevated levels of several cytokines and chemokines upon in vitro culture. This was more pronounced when cells were exposed to additional stimuli in vitro, producing IFN-α, IL-3, IL-6, IL-12, TNF-α, CCL2, CCL3, CCL5, and CXCL8. Following C274 administration in the absence of additional SIV Ag, endogenous IFN-γ secretion was elevated in LN cells of infected animals, but SIV-specific responses were unchanged. Endogenous and SIV-specific responses decreased in blood, before the SIV-specific responses rebounded by 2 wk after C274 treatment. Elevated IFN-α, CCL2, and CCL5 were also detected in the plasma after C274 injection. Thus, locally administered C274 has local and systemic activities, supporting the potential for CpG-C ISS-ODNs to boost immune function to enhance anti-HIV vaccine immunogenicity.

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“…These results demonstrate that pDC from HIV + individuals recognize and respond to the appropriate TLR agonists, but the magnitude of their response to the TLR7 and 7/8 agonists on a per cell basis was significantly less than in uninfected individuals. Infectious and non-infectious AT-2 treated HIV-1 Ada (R5-tropic) and AT-2 treated HIV-1 MN (X4-tropic) virus are potent stimulators of pDC, inducing activation, maturation and secretion of IFN-α (29,30,36). Therefore, in vitro responses to AT-2 inactivated HIV-1 virus were evaluated in PBMC from HIV-1 individuals and compared with responses in uninfected individuals.…”

Section: Hiv-1 and Tlr Agonists Activate Ifn-α Production In Pdc In Tmentioning

confidence: 99%

“…In vitro incubation with HIV-1 can directly activate pDC to produce IFN-α and upregulate CD80 and CD86 expression in cells that have not been exposed to HIV-1 in vivo (29,30). No one has previously determined whether the continued exposure to HIV-1 that takes place during the course of HIV-1 infection alters the ability of DC to respond to HIV-1 or to TLR agonists.…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

Martinson

Román-Gonzaléz

Tenorio

et al. 2007

Cellular Immunology

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We compared TLR responsiveness in PBMC from HIV-1-infected and uninfected individuals using the TLR agonists: TLR7 (3M-001), TLR8 (3M-002) and TLR7/8 (3M-011). Activation and maturation of plasmacytoid dendritic cells (pDC)were measured by evaluating CD86, CD40 and CD83 expression and myeloid dendritic cell (mDC) activation was measured by evaluating CD40 expression. All agonists tested induced activation and maturation of pDC in PBMC cultures of cells from HIV+ and HIV− individuals. The TLR7 agonist induced significantly less pDC maturation in cells from HIV+ individuals. Quantitative assessment of secreted IFN-α and pro-inflammatory cytokines at the single cell level showed that pDC from HIV+ individuals stimulated with TLR7 and TLR7/8 induced IFN-α. TLR8 and TLR7/8 agonists induced IL-12 and COX-2 expression in mDC from HIV+ and HIV− individuals. Understanding pDC and mDC activation and maturation in HIV-1 infection could lead to more rational development of immunotherapeutic strategies to stimulate the adaptive immune response to HIV-1.

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Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type 1 with Alpha Interferon Production and Maturation into Dendritic Cells

Abstract: Natural alpha interferon (IFN-␣)-producing cells (IPCs

Cited by 102 publications

References 39 publications

Immunostimulating capacities of stabilized RNA molecules

Immunostimulating capacities of stabilized RNA molecules

Local and Systemic Effects of Intranodally Injected CpG-C Immunostimulatory-Oligodeoxyribonucleotides in Macaques

Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

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