Cutting Edge: Immune Stimulation by Neisserial Porins Is Toll-Like Receptor 2 and MyD88 Dependent

Abstract

The immunopotentiating activity of neisserial porins, the major outer membrane protein of the pathogenic Neisseria, is mediated by its ability to stimulate B cells and up-regulate the surface expression of B7-2. This ability is dependent on MyD88 and Toll-like receptor (TLR)2 expression, as demonstrated by a lack of a response by B cells from MyD88 or TLR2 knockout mice to the porins. Using previously described TLR2-dependent reporter constructs, these results were confirmed and were shown to be due to induction of NF-κB nuclear translocation. This is the first demonstration of known vaccine adjuvant to stimulate immune cells via TLR2.

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

“…To assess whether the mechanism of adjuvanticity of Nlac PorB was consistent with APC activation, similar to what has been described for Nme PorB [31], we examined its effect on B cells in vitro. Although dendritic cells are mostly responsible for initiation of a primary immune response, activation of both DCs and B cells has been extensively characterized in response to Nme PorB [26,31,32] and is a crucial comparison for the effect of Nlac PorB.…”

“…Murine B cells were isolated from C57Bl/6J mice and C3H/HeJ mice as previously described [31]. Cells were grown in RPMI (Mediatech) containing 10% FBS, 2mM L-glutamine, 100 U/ml penicillin, 100 µg/ml streptomycin, 10 mM HEPES and 10 mM β-ME and defined as R10.…”

“…Although dendritic cells are mostly responsible for initiation of a primary immune response, activation of both DCs and B cells has been extensively characterized in response to Nme PorB [26,31,32] and is a crucial comparison for the effect of Nlac PorB. Purified mouse splenic B cells were incubated with different concentrations of Nlac PorB (20, 10, 1, 0.1 µg/ ml) for 24h and a dose-dependent increase of surface expression of the co-stimulatory molecule CD86, of CD40 and of MHC II was determined by flow cytometry (data not shown).…”

“…Porins from pathogenic Neisseria species have adjuvant activity in humans and animals [34,35]; this is due to activation of antigen presenting cells (APCs), and our group has shown that signaling via Toll-Like receptors (TLRs) [31,32,68] is required for this activity. Increased expression of CD86/CD80, MHC II and CD40 on the APC surface has been shown in response to porins from pathogenic Neisserial species (and other bacteria) [23,26,[30][31][32], as well as B cell proliferation and increased antibody production [33].…”

“…Increased expression of CD86/CD80, MHC II and CD40 on the APC surface has been shown in response to porins from pathogenic Neisserial species (and other bacteria) [23,26,[30][31][32], as well as B cell proliferation and increased antibody production [33]. Activated APCs release specific cytokines (i.e.…”