Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model

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• 作者：Alyssa L. Siefert^a ; ¹ ; Allison Ehrlich^b ; ¹ ; Marí ; a Jesú ; s Corral^c ; Karen Goldsmith-Pestana^b ; Diane McMahon-Pratt^b ; ^{diane.mcmahon-pratt@yale.edu" class="auth_mail" title="E-mail the corresponding author} ; Tarek M. Fahmy^a ; ^d
• 关键词：Nanoparticles ; Leishmaniasis ; Immunotherapy ; CpG ; PAMP ; Parasite
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：108
• 期：Complete
• 页码：168-176
• 全文大小：1017 K

文摘

Leishmania (Viannia) panamensis (L. (V.) panamensis) is a species of protozoan parasites that causes New World leishmaniasis, which is characterized by a hyper-inflammatory response. Current treatment strategies, mainly chemotherapeutic, are suboptimal due to adverse effects, long treatment regimens, and increasing drug resistance. Recently, immunotherapeutic approaches have shown promise in preclinical studies of leishmaniasis. As NPs may enable broad cellular immunomodulation through internalization in phagocytic and antigen-presenting cells, we tested the therapeutic efficacy of biodegradable NPs encapsulating a pathogen-associated molecular pattern (PAMP), CpG-rich oligonucleotide (CpG; NP-CpG), in mice infected with L. (V.) panamensis. NP-CpG treatment reduced lesion size and parasite burden, while neither free CpG nor empty NP showed therapeutic effects. NP-encapsulation led to CpG persistence at the site of infection along with an unexpected preferential cellular uptake by myeloid derived suppressor cells (MDSCs; CD11b⁺Ly6G⁺Ly6C⁻) as well as CD19⁺ dendritic cells. This corresponded with the suppression of the ongoing immune response measured by the reduction of pathogenic cytokines IL-10 and IL-13, as well as IL-17 and IFNγ, in comparison to other treatment groups. As chronic inflammation is generally associated with the accumulation of MDSCs, this study may enable the rational design of cost-effective, safe, and scalable delivery systems for the treatment of inflammation-mediated diseases.