» Articles » PMID: 26840253

The Role of Nitric Oxide and Reactive Oxygen Species in the Killing of Leishmania Braziliensis by Monocytes from Patients with Cutaneous Leishmaniasis

Overview
Journal PLoS One
Date 2016 Feb 4
PMID 26840253
Citations 83
Authors
Affiliations
Soon will be listed here.
Abstract

Human cutaneous leishmaniasis (CL) caused by Leishmania braziliensis, presents an exaggerated Th1 response that is associated with ulcer development. Macrophages are the primary cells infected by Leishmania parasites and both reactive oxygen species (ROS) and nitric oxide (NO) are important in the control of Leishmania by these cells. The mechanism involved in the killing of L. braziliensis is not well established. In this study, we evaluate the role of ROS and NO in the control of L. braziliensis infection by monocytes from CL patients. After in vitro infection with L. braziliensis, the oxidative burst by monocytes from CL patients was higher when compared to monocytes from healthy subjects (HS). Inhibition of the ROS pathway caused a significant decrease in the oxidative burst in L. braziliensis infected monocytes from both groups. In addition, we evaluated the intracellular expression of ROS and NO in L. braziliensis-infected monocytes. Monocytes from CL patients presented high expression of ROS after infection with L. braziliensis. The expression of NO was higher in monocytes from CL patients as compared to expression in monocytes from HS. A strong positive correlation between NO production and lesion size of CL patients was observed. The inhibition of ROS production in leishmania-infected monocytes from CL patients allowed the growth of viable promastigotes in culture supernatants. Thus, we demonstrate that while production of ROS is involved in L. braziliensis killing, NO alone is not sufficient to control infection and may contribute to the tissue damage observed in human CL.

Citing Articles

Cytokine Networks and the Clinical Outcome of American Teg-Umentary Leishmaniasis: Unveiling Targets for Alternative Therapeutic Interventions.

Koh C, Gollob K, Dutra W Pathogens. 2025; 14(2).

PMID: 40005563 PMC: 11858318. DOI: 10.3390/pathogens14020188.


Oxidative stress-driven enhanced iron production and scavenging through Ferroportin reorientation worsens anemia in antimony-resistant Leishmania donovani infection.

Ghosh S, Chigicherla K, Dasgupta S, Goto Y, Mukherjee B PLoS Pathog. 2025; 21(1):e1012858.

PMID: 39888953 PMC: 11785346. DOI: 10.1371/journal.ppat.1012858.


Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules.

de Souza J, Costa N, Brasil M, Dos Anjos L, Barros de Menezes R, Zampieri E Molecules. 2025; 30(2).

PMID: 39860134 PMC: 11768059. DOI: 10.3390/molecules30020264.


Pharmacological inhibition of key metabolic pathways attenuates Leishmania spp infection in macrophages.

de Oliveira E, Tiburcio R, Duarte G, Lago A, de Melo L, Nunes S PLoS Negl Trop Dis. 2025; 19(1):e0012763.

PMID: 39775223 PMC: 11756801. DOI: 10.1371/journal.pntd.0012763.


Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.

Palomino-Cano C, Moreno E, Irache J, Espuelas S Front Immunol. 2024; 15:1437430.

PMID: 39211053 PMC: 11357945. DOI: 10.3389/fimmu.2024.1437430.


References
1.
Almeida R, Lessa H, Bacellar O, Carvalho E . Cytokine profile and pathology in human leishmaniasis. Braz J Med Biol Res. 1998; 31(1):143-8. DOI: 10.1590/s0100-879x1998000100020. View

2.
Almeida T, Palma L, Mendez L, Noronha-Dutra A, Veras P . Leishmania amazonensis fails to induce the release of reactive oxygen intermediates by CBA macrophages. Parasite Immunol. 2012; 34(10):492-8. PMC: 3532614. DOI: 10.1111/j.1365-3024.2012.01384.x. View

3.
Srivastava A, Singh N, Mishra M, Kumar V, Gour J, Bajpai S . Identification of TLR inducing Th1-responsive Leishmania donovani amastigote-specific antigens. Mol Cell Biochem. 2011; 359(1-2):359-68. DOI: 10.1007/s11010-011-1029-5. View

4.
Khouri R, Santos G, Soares G, Costa J, Barral A, Barral-Netto M . SOD1 plasma level as a biomarker for therapeutic failure in cutaneous leishmaniasis. J Infect Dis. 2014; 210(2):306-10. PMC: 4073785. DOI: 10.1093/infdis/jiu087. View

5.
Liew F, Li Y, Millott S . Tumor necrosis factor-alpha synergizes with IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide. J Immunol. 1990; 145(12):4306-10. View