Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages

Lucas Sousa Magalhães; Lays Gisele Santos Bomfim; Camilla Natália Oliveira Santos; Priscila Lima dos Santos; Diego Moura Tanajura; Michael Wheeler Lipscomb; Amélia Ribeiro de Jesus; Roque Pacheco de Almeida; Tatiana Rodrigues de Moura

doi:10.1007/s00436-021-07231-7

Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages

Lucas Sousa Magalhães, Lays Gisele Santos Bomfim, Camilla Natália Oliveira Santos, Priscila Lima dos Santos, Diego Moura Tanajura, Michael Wheeler Lipscomb, Amélia Ribeiro de Jesus, Roque Pacheco de Almeida, Tatiana Rodrigues de Moura

Pharmacology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.

Original language	English (US)
Pages (from-to)	2959-2964
Number of pages	6
Journal	Parasitology Research
Volume	120
Issue number	8
DOIs	https://doi.org/10.1007/s00436-021-07231-7
State	Published - Aug 2021

Bibliographical note

Funding Information:
We appreciate all donor patients for their participation in this study and for support by the Health Sciences Graduate Program from UFS, Brazil.

Funding Information:
Funding institutions: LGSB and CNOS are recipient of Doctoral fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Científico e Tecnológico: 460743/2014–7 (TRM) and 552721/2011–5 (RPA); Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe: 019.203.02712/2009–8 (ARJ). LSM is postdoctoral fellow in Instituto de Investigação em Imunologia (iii)/CAPES.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

Leishmania infantum
Macrophages
Meglumine antimoniate
Visceral leishmaniasis

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10.1007/s00436-021-07231-7

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title = "Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages",

abstract = "Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.",

keywords = "Leishmania infantum, Macrophages, Meglumine antimoniate, Visceral leishmaniasis",

author = "Magalh{\~a}es, {Lucas Sousa} and Bomfim, {Lays Gisele Santos} and Santos, {Camilla Nat{\'a}lia Oliveira} and {dos Santos}, {Priscila Lima} and Tanajura, {Diego Moura} and Lipscomb, {Michael Wheeler} and {de Jesus}, {Am{\'e}lia Ribeiro} and {de Almeida}, {Roque Pacheco} and {de Moura}, {Tatiana Rodrigues}",

note = "Funding Information: We appreciate all donor patients for their participation in this study and for support by the Health Sciences Graduate Program from UFS, Brazil. Funding Information: Funding institutions: LGSB and CNOS are recipient of Doctoral fellowship from Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior (CAPES); Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico: 460743/2014–7 (TRM) and 552721/2011–5 (RPA); Funda{\c c}{\~a}o de Apoio {\`a} Pesquisa e {\`a} Inova{\c c}{\~a}o Tecnol{\'o}gica do Estado de Sergipe: 019.203.02712/2009–8 (ARJ). LSM is postdoctoral fellow in Instituto de Investiga{\c c}{\~a}o em Imunologia (iii)/CAPES. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2021",

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doi = "10.1007/s00436-021-07231-7",

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AU - Magalhães, Lucas Sousa

AU - Bomfim, Lays Gisele Santos

AU - Santos, Camilla Natália Oliveira

AU - dos Santos, Priscila Lima

AU - Tanajura, Diego Moura

AU - Lipscomb, Michael Wheeler

AU - de Jesus, Amélia Ribeiro

AU - de Almeida, Roque Pacheco

AU - de Moura, Tatiana Rodrigues

N1 - Funding Information: We appreciate all donor patients for their participation in this study and for support by the Health Sciences Graduate Program from UFS, Brazil. Funding Information: Funding institutions: LGSB and CNOS are recipient of Doctoral fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Científico e Tecnológico: 460743/2014–7 (TRM) and 552721/2011–5 (RPA); Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe: 019.203.02712/2009–8 (ARJ). LSM is postdoctoral fellow in Instituto de Investigação em Imunologia (iii)/CAPES. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2021/8

Y1 - 2021/8

N2 - Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.

AB - Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.

KW - Leishmania infantum

KW - Macrophages

KW - Meglumine antimoniate

KW - Visceral leishmaniasis

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ER -

Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages

Abstract

Bibliographical note

Keywords

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