Staphylococcus aureus-Induced Plasmacytoid Dendritic Cell Activation Is Based on an IgG-Mediated Memory Response

Abstract

Type I IFNs represent a major antimicrobial defense mechanism due to their property of enhancing immune responses by priming both innate and adaptive immune cells. Plasmacytoid dendritic cells (pDC) are the major source of type I IFN in the human body and represent innate immune cells involved in first-line defense against invading pathogens. Although pDC activation has been extensively studied upon stimulation with synthetic TLR ligands, viruses, and intracellular bacteria, there is only scarce information on extracellular bacteria. In this study we show that the triggering of human pDC-derived IFN-α secretion by Staphylococcus aureus is independent of TLR2 and specific for coagulase-positive staphylococci. Specificity of the pDC response to S. aureus is independent of the bacterial virulence factors protein A and α-toxin but is mediated by Ag-specific IgG and CD32. S. aureus-induced pDC activation can be blocked by inhibitory DNA oligonucleotides and chloroquine, suggesting that engagement of TLR7/9 by bacterial nucleic acids after CD32-mediated uptake of these compounds may play a central role in this process. Altogether, we propose that in marked contrast to nonselective TLR2-dependent activation of most innate immune cells, pDC activation by S. aureus represents an Ag-specific memory response since it requires the presence of class-switched immunoglobulins.

Human Plasmacytoid Dendritic Cells Phagocytose, Process, and Present Exogenous Particulate Antigen

“…In this study, we investigated whether pDCs can play a role in immune responses against exogenous particulates. Up to now, it was highly controversial whether pDCs are able to respond to stimuli entrapped in particle-like structures (3,8,9,14,(16)(17)(18)(19). We demonstrate that pDCs are clearly capable of phagocytosing Ag entrapped within PLGA microparticles and subsequent processing of the encapsulated Ag.…”

“…However, Piccioli and coworkers (3) postulate that pDCs cannot phagocytose bacteria (Staphylococcus aureus and Escherichia coli) and require myeloid DCs to respond to bacterial stimuli. On the contrary, other studies show that pDCs can be activated by extracellular bacteria (S. aureus and Streptococcus pyogenes), but it was not established whether this was due to uptake of entire bacteria or mere bacterial components (8,9). Furthermore, most vaccines, such as live attenuated or inactivated pathogen-based formulations, lipid emulsions, biocompatible and biodegradable nano-and microparticles, immunostimulatory complexes, virosomes, and virus-like particles, are particulate in nature and favor delivery of antigenic cargo and/or immunostimulatory molecules to phagocytic APCs, such as myeloid and monocyte-derived DCs (moDCs) (20)(21)(22)(23).…”

“…Although unstimulated pDCs promote an unbiased Th or a Th2 response, activated pDCs promote DC activation and trigger a Th1 response (5-7). Recently, it was shown that not only viruses, but also whole live bacteria can induce pDC activation, resulting in Th1 polarization of naive CD4 + T cells (8,9). Furthermore, pDCs can interact synergistically with myeloid DCs by enhancing their priming ability in a contact-dependent manner, resulting in increased levels of Ag-specific CTLs (3,10).…”

Induction of Type I IFN Is a Physiological Immune Reaction to Apoptotic Cell-Derived Membrane Microparticles

“…Despite this, only a few studies have investigated their actual role in the immune response. These studies defined pDC as vital cellular components in the initiation of NK and T cell responses to viral Ags (11,12), effectors in the memory response to microbial Ags, where Ag-specific IgG is a prerequisite for pDC activation (13,14), important mediators of transplant tolerance (15)(16)(17)(18), and inducers of T regulatory cells (19,20).…”

Antibacterial activity of different extracts from theCatharanthus roseus

“…The cultures were maintained on the nutrient agar slant. The Bacillus subtilis [11] Staphylococcus aureus [12][13][14] Streptococcus pyogenes [15][16] Streptococcus agalactiae [17][18] Corynebacterium diphtheriae [19][20] Escherichia coli [21][22] Pseudomonas aeruginosa [23][24] Salmonella typhi [25][26] Shigella boydii [27][28] Aeromonas hydrophila [29][30] nutrient agar was poured into the perti plates (10 × 10cm) and allowed to solidify, after solidification, it was kept in the incubator at 37°C for 24 hours. The main reason for incubation was to maintain the sterility.…”