Tailoring the immune response by targeting C-type lectin receptors on alveolar macrophages using 鈥減athogen-like鈥?amphiphilic polyanhydride nanoparticles

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• 作者：Ana V. Chavez-Santoscoy^a ; Rajarshi Roychoudhury^b ; Nicola L.B. Pohl^a ; ^b ; Michael J. Wannemuehler^c ; Balaji Narasimhan^a ; ^{nbalaji@iastate.edu} ; Amanda E. Ramer-Tait^c
• 关键词：Polyanhydrides ; Nanoparticles ; Carbohydrates ; Alveolar macrophages
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：June, 2012
• 卷：33
• 期：18
• 页码：4762-4772
• 文件大小：1270 K

摘要

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 (AM蠒), a principle respiratory tract APC. Co-culture of functionalized nanoparticles with AM蠒 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 AM蠒 activation phenotype was found to be dependent upon nanoparticle internalization. Functionalization also promoted increased AM蠒 production of the pro-inflammatory cytokines IL-1尾, IL-6 and TNF-伪. 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.