The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation

  title={The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation},
  author={Michaela Reiser and Munir M. Mosaheb and Christina Lisk and Andrew M. Platt and Lee M. Wetzler},
  journal={Scientific Reports},
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… 
Neisserial PorB immune enhancing activity and use as a vaccine adjuvant
The work presented here provides examples of the mechanistic studies required to understand how vaccine adjuvants are contributing to the establishment of protective immunity.
CD169+ Subcapsular Macrophage Role in Antigen Adjuvant Activity
It is demonstrated that macrophage expression of MyD88 (required for TLR2 signaling) is an absolute requirement for the improved antibody response induced by PorB, and this study investigated the role of subcapsular CD169+ marginal zone macrophages in antibody production induced by the use of TLR-ligand based adjuvants.
Toll-Like Receptor Ligand Based Adjuvant, PorB, Increases Antigen Deposition on Germinal Center Follicular Dendritic Cells While Enhancing the Follicular Dendritic Cells Network
PorB is the only adjuvant tested that induces both a higher number of FDCs and increased deposition of antigen on F DCs, and has the greatest ability to increase FDC-antigen interaction, essential for induction of B cell affinity maturation.
Cross-presentation of Exogenous Antigens.
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Bacterial Protein Toll-Like-Receptor Agonists: A Novel Perspective on Vaccine Adjuvants
Protein adjuvants can be genetically fused to protein antigens which ensure the co-delivery of adjuvant-antigen not only into the same cell but also in the same endocytic cargo, leading to more effective activation of innate and adaptive immune response.
Bioconjugation Approaches to Producing Subunit Vaccines Composed of Protein or Peptide Antigens and Covalently Attached Toll-Like Receptor Ligands.
Various TLR agonists utilized as immunostimulatory adjuvants are summarized and the development of techniques for generating adjuvant-antigen fusion vaccines incorporating peptide or protein antigens is focused on.
Development of an Enzyme-Mediated, Site-Specific Method to Conjugate Toll-Like Receptor 2 Agonists onto Protein Antigens: Towards a Broadly Protective, Four Component, Group A Streptococcal Self-Adjuvanting Lipoprotein-Fusion Combination Vaccine.
A conjugation platform is established that allows for the production of defined, site-specific antigen-adjuvant conjugates, which maintain the native three-dimensional structure of antigens, and can be potentially applied to a variety of protein antIGens.
Toll‐like receptor‐2/7‐mediated T cell activation: An innate potential to augment CD8+ T cell cytokine production
Combined TCR and TLR triggering enhances the proliferation, memory formation and effector function of T cells, resulting in enhanced production of interferon γ, tumour necrosis factor α and interleukin 2.
Immunoenhancement of recombinant Neisseria meningitides PorB protein on porcine circovirus type 2 and Mycoplasma hyopneumo-niae genetically engineered vaccines.
The recombinant protein PorB may be a good candidate adjuvant for improving the protective effect of vaccines against porcine circovirus type 2 and Mycoplasma hyopneumoniae, and the protein can be used for future practical applications.


Neisserial Porin-Induced Dendritic Cell Activation Is MyD88 and TLR2 Dependent1
PorB treatment induced DC maturation, and not only enhanced the allostimulatory activity of DC, but also augmented the ability of DC to stimulate T cells in an Ag-specific manner, which may have implications for the adjuvant property of porin.
In Vivo and In Vitro Characterization of the Immune Stimulating Activity of the Neisserial Porin PorB
Vaccines play a vital role in modern medicine. The development of novel vaccines for emerging and resistant pathogens has been aided in recent years by the use of novel adjuvants in subunit vaccines.
TLR ligands differentially affect uptake and presentation of cellular antigens.
It is demonstrated that stimulation of monocyte-derived DCs with Toll-like receptor (TLR) ligands differentially affects the uptake and cross-presentation of cellular antigens.
CD8+ T Cell Immunodominance in Lymphocytic Choriomeningitis Virus Infection Is Modified in the Presence of Toll-Like Receptor Agonists
The data demonstrate a novel role for TLR ligands in regulating antiviral CD8+ T cell responses due to the regulation of the cross-presentation of cell-associated antigens.
Toll-dependent selection of microbial antigens for presentation by dendritic cells
It is shown that the efficiency of presenting antigens from phagocytosed cargo is dependent on the presence of TLR ligands within the cargo and the generation of peptide–MHC class II complexes is controlled by TLRs in a strictly phagosome-autonomous manner.
A Subset of Toll-Like Receptor Ligands Induces Cross-presentation by Bone Marrow-Derived Dendritic Cells1
Using DCs and CTLs in an in vitro cross- presentation system, it is shown that a subset of microbial TLR ligands, namely ligands of TLR3 (poly(inosinic-cytidylic) acid) and TLR9 (immunostimulatory CpG DNA), induces cross-presentation.
Neisserial Porins Induce B Lymphocytes to Express Cost imulatory B 7-2 Molecules and to Proliferate
Upregulation of B7-2 on the surface o fB lymphocytes may be the mechanism behind the immunopotentiating activity of neisserial porins.
Cutting Edge: The RIG-I Ligand 3pRNA Potently Improves CTL Cross-Priming and Facilitates Antiviral Vaccination
Triphosphate RNA (3pRNA) is a superior adjuvant for CTL activation and might be useful to facilitate antiviral immunization strategies.
The role of B/T costimulatory signals in the immunopotentiating activity of neisserial porin.
The hypothesis that the ability of neisserial porins to improve the immune response to poorly immunogenic antigens is related to porin-induced increases in B7-2 expression on antigen-presenting cells and enhanced B/T cell interactions is supported.