Abstract
TOLL-like receptor (TLR) ligands activate both innate and adaptive immune cells, while modulating the cellular immune response. The outer membrane protein (OMP) from Neisseria meninigitidis, PorB, is a naturally occurring TLR2 ligand and functions as an adjuvant. Here, we demonstrate that PorB increases the level of OVA in the endo-/lysosomal cellular compartment of BMDCs, increases antigen presenting cell (APC) trafficking to draining lymph nodes, and enhances antigen cross-presentation. PorB is capable of mounting an antigen specific T cell response by efficiently stimulating antigen cross-presentation in vivo and in vitro assessed by BMDC OT-I cocultivation assays. The enhanced antigen cross-presentation and the increased APC recruitment to secondary lymphoid tissues expand the scope of known adjuvant effects of PorB on the immune system. Our findings lead to a better understanding of how TLR-ligand based adjuvants can alter and modulate immune responses.
Highlights
CD4 T cells, whereas CD8α+ DCs present exogenous antigen in context of MHC class I to CD8 T cells, a process called cross-presentation[17,18,19]
Antigen uptake was analyzed by flow cytometry and interpreted as mean fluorescence intensity (MFI) of OVA-A594 associated with CD11c+ CD11b+ bone marrow derived dendritic cells (BMDCs) (Supplementary Fig. S1a for gating strategy)
We found no difference in antigen uptake in TLR2−/− BMDCs (Supplementary Fig. S1b) comparing OVA-A594 + PorB with OVA-A594 only treated BMDCs
Summary
CD4 T cells, whereas CD8α+ DCs present exogenous antigen in context of MHC class I to CD8 T cells, a process called cross-presentation[17,18,19]. Many investigators, including us, have shown, that PorB acts as a potent adjuvant and induces a robust immune response, when co-administered with poorly immunogenic antigens, e.g. peptides[21] or ovalbumin[22]. PorB has been shown to be able to induce a T cell-dependent response to normally T cell-independent antigens, like bacterial capsular polysaccharides (CPS)[23,24,25,26]. Our group has shown that PorB enhances the humoral immune response to the meningococcal CPS, which is dependent on increased expression of CD86 on APCs27. In the present study we investigated how PorB modulates antigen localization within professional APCs using in vitro matured bone marrow derived dendritic cells (BMDCs) stimulated with fluorescently labeled ovalbumin (OVA). Our findings support the potential of PorB being used as a TLR based adjuvant in vaccine formulations
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