TY - JOUR
T1 - Tailoring the immune response by targeting C-type lectin receptors on alveolar macrophages using " pathogen-like" amphiphilic polyanhydride nanoparticles
AU - Chavez-Santoscoy, Ana V.
AU - Roychoudhury, Rajarshi
AU - Pohl, Nicola L.B.
AU - Wannemuehler, Michael J.
AU - Narasimhan, Balaji
AU - Ramer-Tait, Amanda E.
N1 - Funding Information:
The authors would like to thank the United States Army Medical Research and Materiel Command for financial support (Grant No. W81XWH-10-1-0806 ). The authors are grateful to Shawn Rigby for his expertise in flow cytometry and to Dr. Mary Ann McDowell of the University of Notre Dame for generously providing the MMR −/− mice. BN acknowledges the Balloun Professorship in Chemical and Biological Engineering and NLBP acknowledges the Wilkinson Professorship of Interdisciplinary Engineering.
PY - 2012/6
Y1 - 2012/6
N2 - C-type lectin receptors (CLRs) offer unique advantages for tailoring immune responses Engagement of CLRs regulates antigen presenting cell (APC) activation and promotes delivery of antigens to specific intracellular compartments inside APCs for efficient processing and presentation In these studies, we have designed an approach for targeted antigen delivery by decorating the surface of polyanhydride nanoparticles with specific carbohydrates to provide pathogen-like properties Two conserved carbohydrate structures often found on the surface of respiratory pathogens, galactose and di-mannose, were used to functionalize the surface of polyanhydride nanoparticles and target CLRs on alveolar macrophages (AMφ), a principle respiratory tract APC Co-culture of functionalized nanoparticles with AMφ significantly increased cell surface expression of MHC I and II, CD86, CD40 and the CLR CIRE over non-functionalized nanoparticles Di-mannose and galactose functionalization also enhanced the expression of the macrophage mannose receptor (MMR) and the macrophage galactose lectin, respectively This enhanced AMφ activation phenotype was found to be dependent upon nanoparticle internalization Functionalization also promoted increased AMφ production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α Additional studies demonstrated the requirement of the MMR for the enhanced cellular uptake and activation provided by the di-mannose functionalized nanoparticles Together, these data indicate that targeted engagement of MMR and other CLRs is a viable strategy for enhancing the intrinsic adjuvant properties of nanovaccine adjuvants and promoting robust pulmonary immunity.
AB - C-type lectin receptors (CLRs) offer unique advantages for tailoring immune responses Engagement of CLRs regulates antigen presenting cell (APC) activation and promotes delivery of antigens to specific intracellular compartments inside APCs for efficient processing and presentation In these studies, we have designed an approach for targeted antigen delivery by decorating the surface of polyanhydride nanoparticles with specific carbohydrates to provide pathogen-like properties Two conserved carbohydrate structures often found on the surface of respiratory pathogens, galactose and di-mannose, were used to functionalize the surface of polyanhydride nanoparticles and target CLRs on alveolar macrophages (AMφ), a principle respiratory tract APC Co-culture of functionalized nanoparticles with AMφ significantly increased cell surface expression of MHC I and II, CD86, CD40 and the CLR CIRE over non-functionalized nanoparticles Di-mannose and galactose functionalization also enhanced the expression of the macrophage mannose receptor (MMR) and the macrophage galactose lectin, respectively This enhanced AMφ activation phenotype was found to be dependent upon nanoparticle internalization Functionalization also promoted increased AMφ production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α Additional studies demonstrated the requirement of the MMR for the enhanced cellular uptake and activation provided by the di-mannose functionalized nanoparticles Together, these data indicate that targeted engagement of MMR and other CLRs is a viable strategy for enhancing the intrinsic adjuvant properties of nanovaccine adjuvants and promoting robust pulmonary immunity.
KW - Alveolar macrophages
KW - Carbohydrates
KW - Nanoparticles
KW - Polyanhydrides
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U2 - 10.1016/j.biomaterials.2012.03.027
DO - 10.1016/j.biomaterials.2012.03.027
M3 - Article
C2 - 22465338
AN - SCOPUS:84859830991
SN - 0142-9612
VL - 33
SP - 4762
EP - 4772
JO - Biomaterials
JF - Biomaterials
IS - 18
ER -