Dendritic Cell Recruiter: A Pathogen-Agnostic Immune Enhancer for Broad-Spectrum Antimicrobial Protection

Abstract

As emerging pathogens and antimicrobial resistance are increasing in prevalence, pathogen-agnostic, broad-spectrum therapeutics are urgently needed to address growing threats to public health. Here, we report a novel immune response-enhancing biomaterial that targets dendritic cells to activate innate immunity and strengthen the host defense to any potential pathogen. This biomaterial with therapeutic potential consists of a previously demonstrated dendritic cell-binding peptide (DC) conjugated to nanofibers formed by the self-assembling peptide, Q11. Antibody-based binding assays and computational modeling demonstrated that incorporation of DC-Q11 at 5% relative to unconjugated Q11 optimizes the surface presentation and allowed maximum accessibility of the DC peptide on these nanofibers for biological applications. DC-functionalized Q11 nanofibers promoted dendritic cell maturation, as evidenced by an increase in cell surface receptor expression profile, elevated proinflammatory cytokine production, and a decrease in anti-inflammatory cytokines. Further in vivo evaluation of this material construct could provide a more comprehensive understanding of its potential as a broad-spectrum therapeutic agent. Collectively, utilization of supramolecular materials platform, antibody engineering, and cellular assay techniques described herein might facilitate future research toward the development of broad-spectrum immunotherapeutic applications.