Pubfacts - Scientific Publication Data
  • Categories
  • |
  • Journals
  • |
  • Authors
  • Login
  • Categories
  • Journals

Search Our Scientific Publications & Authors

Publications
  • Publications
  • Authors
find publications by category +
Translate page:

Photodynamic inactivation of Leishmania braziliensis doubly sensitized with uroporphyrin and diamino-phthalocyanine activates effector functions of macrophages in vitro.

Authors:
Rohit Sharma Sayonara M Viana Dennis K P Ng Bala K Kolli Kwang Poo Chang Camila I de Oliveira

Sci Rep 2020 10 13;10(1):17065. Epub 2020 Oct 13.

Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74154-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555832PMC
October 2020

Publication Analysis

Top Keywords

braziliensis
9
doubly sensitized
8
red light
8
leishmania subgenus
8
braziliensis transfectants
8
photodynamically inactivated
8
effector functions
8
inactivation leishmania
8
functions macrophages
8
photodynamic inactivation
8
macrophages
7
leishmania
6
independent clones
4
clones invariably
4
invariably ala-responsive
4
study independent
4
marked il10
4
deficiencies porphyrin/heme
4
porphyrin/heme biosynthesis
4
biosynthesis study
4

Keyword Occurance

Similar Publications

Autochthonous and imported tegumentary leishmaniasis in Catalonia (Spain): aetiological evolution in the last four decades and usefulness of different typing approaches based on biochemical, molecular and proteomic markers.

Authors:
Anna Fernández-Arévalo Cristina Ballart Jordana Muñoz-Basagoiti Leire Basarte Gonzalo Lobato Albert Arnau Alba Abras Silvia Tebar Teresa Llovet Patrick Lami Francine Pratlong Mercè Alsina Esther Roe Lluís Puig Carme Muñoz Montserrat Gállego

Transbound Emerg Dis 2021 Apr 17. Epub 2021 Apr 17.

Secció de Parasitologia, Departament de Biologia, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Sanitat i Medi Ambient, Barcelona, Spain.

Leishmaniasis is a transmissible disease caused by Leishmania protozoa. Spain is endemic for both visceral and cutaneous leishmaniasis, the autochthonous aetiological agent being Leishmania infantum. Around the world, the L. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

Constitutive nitric oxide synthase-like enzyme in two species involved in cutaneous and mucocutaneous leishmaniasis.

Authors:
Rodrigo R Furtado Dara C Soares Alejandro F Prado Luis H S Farias Bruno J M Da Silva Ana P D Rodrigues Edilene O Silva

Parasitol Int 2021 Apr 13:102347. Epub 2021 Apr 13.

Federal University of Para, Institute of Biological Sciences, Laboratory of Structural Biology, Belém 66095-110, Pará, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, 21.941-902 Rio de Janeiro, Brazil. Electronic address:

Leishmania is an obligate intracellular parasite that primarily inhabits macrophages. The destruction of the parasite in the host cell is a fundamental mechanism for infection control. In addition, inhibition of the leishmanicidal activity of macrophages seems to be related to the ability of some species to inhibit the production of nitric oxide (NO) by depleting arginine. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

Dual Role of Insulin-Like Growth Factor (IGF)-I in American Tegumentary Leishmaniasis.

Authors:
Carolina de O Mendes-Aguiar Camilla Lopes-Siqueira Fabrício Pettito-Assis Márcia Pereira-Oliveira Manoel Paes de Oliveira-Neto Claude Pirmez Alda Maria Da-Cruz Hiro Goto

J Immunol Res 2021 29;2021:6657785. Epub 2021 Mar 29.

Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Background: Cytokines and growth factors involved in the tissue inflammatory process influence the outcome of infection. Insulin-like growth factor (IGF-I) constitutively present in the skin may participate in the inflammatory process and parasite-host interaction. Previous work has shown that preincubation of () with recombinant IGF-I induces accelerated lesion development. Read More

View Article and Full-Text PDF
March 2021
Similar Publications

Genome sequence of Vibrio fluvialis 362.3 isolated from coral Mussismilia braziliensis reveals genes related to marine environment adaptation.

Authors:
Livia M R Vidal Aline R P Gonçalves Tainá M Venas Gizele D Garcia Diogo A Tschoeke Fabiano L Thompson Cristiane C Thompson

Arch Microbiol 2021 Apr 7. Epub 2021 Apr 7.

Institute of Biology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.

Vibrio fluvialis is a halophilic bacterium frequently found in estuarine and coastal waters environments. The strain 362.3 was isolated from Mussismilia braziliensis coral of Abrolhos Bank. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

Efficient photodynamic inactivation of Leishmania parasites mediated by lipophilic water-soluble Zn(II) porphyrin ZnTnHex-2-PyP.

Authors:
Tiago H S Souza Camila G Andrade Fernanda V Cabral José F Sarmento-Neto Júlio S Rebouças Beate S Santos Martha S Ribeiro Regina C B Q Figueiredo Adriana Fontes

Biochim Biophys Acta Gen Subj 2021 Mar 31:129897. Epub 2021 Mar 31.

Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, PE, Brazil. Electronic address:

Background: Photodynamic inactivation (PDI) is emerging as a promising alternative for cutaneous leishmaniasis (CL). The chemotherapy currently used, presents adverse effects and cases of drug resistance have been reported. ZnTnHex-2-PyP is a porphyrin with a high potential as a photosensitizer (PS) for PDI, due to its photophysical properties, structural stability, and cationic/amphiphilic character that can enhance interaction with cells. Read More

View Article and Full-Text PDF
March 2021
Similar Publications
© 2021 PubFacts.
  • About PubFacts
  • Privacy Policy
  • Sitemap