From Secretome Analysis to Immunology

Abstract

Dendritic cells are known to be activated by a wide range of microbial products, leading to cytokine production and increased levels of membrane markers such as major histocompatibility complex class II molecules. Such activated dendritic cells possess the capacity to activate naïve T cells. In the present study we demonstrated that immature dendritic cells secrete both the YM1 lectin and lipocalin-2. By testing the ligands of these two proteins, chitosan and siderophores, respectively, we also demonstrated that chitosan, a degradation product of various fungal and protozoal cell walls, induces an activation of dendritic cells at the membrane level, as shown by the up-regulation of membrane proteins such as class II molecules, CD80 and CD86 via a TLR4-dependent mechanism, but is not able to induce cytokine production. This led to the production of activated dendritic cells unable to stimulate T cells. However, costimulation with other microbial products overcame this partial activation and restored the capacity of these activated dendritic cells to stimulate T cells. In addition, successive stimulation with chitosan and then by lipopolysaccharide induced a dosedependent change in the cytokinic IL-12/IL-10 balance produced by the dendritic cells.

The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons

“…We demonstrated that type I IFNs are crucial for the adjuvanticity of chitosan, both in its ability to promote DC activation in vitro and its ability to enhance cell-mediated immunity in vivo. This observation contrasts with a previous report which proposes a role for TLR4 in chitosan-mediated DC activation (Villiers et al, 2009). We and others have demonstrated the inflammasome-activating potential of chitosan (Bueter et al, 2011, 2014; Mori et al, 2012).…”

Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes

“…However, as with MC-derived particles, some synthetic particles are able to persist within the tissue (data not shown), and these may also promote the function of encapsulated cytokines at the site of injection. Furthermore, although chitosan has been suggested to promote some level of innate immune activation 23 , we find here that particles made from this highly purified chitosan do not, alone, have adjuvant activity, and this property emerges only when the particles are used as carriers for immuno-modulatory cytokines.…”

“…Responses were also compared with mice administered HA emulsified in the standard vaccine adjuvant, alum, as a positive control. As other groups have reported that chitosan is able to induce innate immune activation on a cellular level 23 , and that different formulations of chitosan complexes have adjuvant activity 24,25 , we included a further control where mice were given HA in combination with empty particles, consisting of only the heparin–chitosan core. We then stained single-cell suspensions from the draining LN for the cellular activation marker of germinal centres, GL7, for quantification by flow cytometry.…”

Chitosan oligosaccharide affects antioxidant defense capacity and placental amino acids transport of sows

“…As a natural polysaccharide, COS is the depolymerized product of chitosan, and has good solubility in water and various biological activities, including immune-stimulant [5], anti-inflammatory [6] and antioxidant properties [7]. Numerous studies have shown that chitosan has beneficial effects on relieving the oxidative stress [8].…”