CD169+ Subcapsular Macrophage Role in Antigen Adjuvant Activity

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Effective vaccines are critical for public health, but many infectious diseases still lack adequate immunization strategies.
• Toll-like receptor (TLR) ligands, such as Neisseria meningitidis outer membrane protein PorB, are investigated as immune-enhancing adjuvants.
• PorB adjuvant activity involves increased costimulatory factors on antigen-presenting cells (APCs), enhanced antigen-specific antibody production, and elevated cytokine-producing T cells, with MyD88 signaling being essential.

Purpose of the Study:

• To investigate the role of subcapsular CD169+ marginal zone macrophages in antibody production induced by TLR-ligand (PorB, CpG) and non-TLR-ligand (aluminum salts) adjuvants.
• To examine the impact of CD169+ macrophage depletion on antigen and APC trafficking to lymph nodes following adjuvant administration.

Main Methods:

• Utilized CD169 knockout mice and clodronate-treated mice (depleting marginal zone macrophages) to assess adjuvant-dependent antibody production.
• Quantified total antigen-specific immunoglobulins (IgGs) to evaluate antibody responses.
• Employed immunofluorescence to analyze antigen loading on dendritic cells (DCs) and antigen deposition on follicular dendritic cells (FDCs) in lymph nodes.

Main Results:

• Depletion of CD169+ macrophages reduced total IgG production across all adjuvant types, with the greatest reduction observed with TLR ligands (PorB and CpG).
• PorB-containing vaccines showed significantly decreased antigen deposition in lymphoid follicles and germinal centers in CD169-deficient or depleted mice.
• CpG adjuvants led to reduced FDC networks in clodronate-treated mice, while alum adjuvants primarily affected IgG levels in CD169 knockout mice.

Conclusions:

• Subcapsular CD169+ macrophages play a vital role in adjuvant-mediated antibody production.
• The observed effects suggest that TLR-ligand adjuvants, particularly PorB, influence antigen trafficking to lymph nodes and subsequent deposition on FDCs.
• These findings highlight the importance of subcapsular macrophages in optimizing vaccine adjuvant function and overall immunogenicity.