دورية أكاديمية
Photodynamic inactivation of Leishmania braziliensis doubly sensitized with uroporphyrin and diamino-phthalocyanine activates effector functions of macrophages in vitro.
| العنوان: | Photodynamic inactivation of Leishmania braziliensis doubly sensitized with uroporphyrin and diamino-phthalocyanine activates effector functions of macrophages in vitro. |
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| المؤلفون: | Sharma R; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil., Viana SM; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil., Ng DKP; Chinese University of Hong Kong, Shatin, Hong Kong., Kolli BK; Chicago Medical School/Rosalind Franklin University of Medicine & Science, North Chicago, IL, 60064, USA., Chang KP; Chicago Medical School/Rosalind Franklin University of Medicine & Science, North Chicago, IL, 60064, USA., de Oliveira CI; Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil. camila.indiani@fiocruz.br.; INCT-Instituto de Investigação Em Imunologia, São Paulo, Brazil. camila.indiani@fiocruz.br. |
| المصدر: | Scientific reports [Sci Rep] 2020 Oct 13; Vol. 10 (1), pp. 17065. Date of Electronic Publication: 2020 Oct 13. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Indoles/*pharmacology , Leishmania braziliensis/*drug effects , Leishmania braziliensis/*radiation effects , Macrophages/*immunology , Macrophages/*parasitology , Photosensitizing Agents/*pharmacology , Uroporphyrins/*pharmacology, Aminolevulinic Acid/pharmacology ; Animals ; Animals, Genetically Modified ; Female ; Humans ; Immunity, Innate ; In Vitro Techniques ; Isoindoles ; Leishmania braziliensis/immunology ; Leishmaniasis, Cutaneous/immunology ; Leishmaniasis, Cutaneous/prevention & control ; Mice ; Mice, Inbred BALB C ; Protozoan Vaccines/immunology ; Ultraviolet Rays |
| مستخلص: | Photodynamic inactivation of Leishmania has been shown to render them non-viable, but retain their immunological activities. Installation of dual photodynamic mechanisms ensures complete inactivation of species in the Leishmania subgenus, raising the prospect of their safe and effective application as whole-cell vaccines against leishmaniasis. Here, we report the successful extension of this approach to L. braziliensis in the Viannia subgenus, viz. genetic engineering of promastigotes for cytosolic accumulation of UV-sensitive uroporphyrin (URO) and their loading with red light excitable phthalocyanines (PC) that was cationized by chemical engineering. The transgenic strategy used previously produced L. braziliensis transfectants, which gave the same phenotype of aminolevulinate (ALA)-inducible uroporphyria as found in Leishmania subgenus, indicative of pre-subgenus evolutionary origin for similar genetic deficiencies in porphyrin/heme biosynthesis. In the present study, 12 independent clones were obtained and were invariably ALA-responsive, albeit to different extent for uroporphyrinogenesis and UV-inactivation. In a separate study, L. braziliensis was also found, like other Leishmania spp., to take up diamino-PC (PC2) for red light inactivation. In vitro interactions of a highly uroporphyrinogenic clone with primary macrophages were examined with the intervention of URO/PC2-medated double-photodynamic inactivation to ascertain its complete loss of viability. Doubly sensitized L. braziliensis transfectants were photo-inactivated before (Strategy #1) or after (Strategy #2) loading of macrophages. In both cases, macrophages were found to take up L. braziliensis and degrade them rapidly in contrast to live Leishmania infection. The effector functions of macrophages became upregulated following their loading with L. braziliensis photodynamically inactivated by both strategies, including CD86 expression, and IL6 and NO production. This was in contrast to the immunosuppressive infection of macrophages with live parasites, marked by IL10 production. The results provide evidence that photodynamically inactivated L. braziliensis are susceptible to the degradative pathway of macrophages with upregulation of immunity relevant cytokine and co-stimulatory markers. The relative merits of the two loading strategies with reference to previous experimental vaccination were discussed in light of the present findings with L. braziliensis. |
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| المشرفين على المادة: | 0 (Indoles) 0 (Isoindoles) 0 (Photosensitizing Agents) 0 (Protozoan Vaccines) 0 (Uroporphyrins) 88755TAZ87 (Aminolevulinic Acid) V5PUF4VLGY (phthalocyanine) |
| تواريخ الأحداث: | Date Created: 20201014 Date Completed: 20210126 Latest Revision: 20211204 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7555832 |
| DOI: | 10.1038/s41598-020-74154-1 |
| PMID: | 33051524 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2045-2322 |
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| DOI: | 10.1038/s41598-020-74154-1 |