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Leishmania amazonensis from distinct clinical forms/hosts has polymorphisms in Lipophosphoglycans, displays variations in immunomodulatory properties and, susceptibility to antileishmanial drugs

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Rego, Felipe D. ; Cardoso, Camila D. A. ; Moreira, Paulo Otavio L. ; Nogueira, Paula M. ; Araujo, Marcio S. ; Borges, Valeria Matos ; Laurenti, Marcia D. ; Bartholomeu, Daniella C. ; Reis, Alexandre B. ; Monte-Neto, Rubens L. D. ; Soares, Rodrigo P.
Total Authors: 11
Document type: Journal article
Source: Cell Biology International; v. 46, n. 11, p. 12-pg., 2022-08-23.
Abstract

Lipophosphoglycan (LPG), the major Leishmania glycoconjugate, induces pro-inflammatory/immunosuppressive innate immune responses. Here, we evaluated functional/biochemical LPG properties from six Leishmania amazonensis strains from different hosts/clinical forms. LPGs from three strains (GV02, BA276, and LV79) had higher pro-inflammatory profiles for most of the mediators, including tumor necrosis factor alpha and interleukin 6. For this reason, glycoconjugates from all strains were biochemically characterized and had polymorphisms in their repeat units. They consisted of three types: type I, repeat units devoid of side chains; type II, containing galactosylated side chains; and type III, containing glucosylated side chains. No relationship was observed between LPG type and the pro-inflammatory properties. Finally, to evaluate the susceptibility against antileishmanial agents, two strains with high (GV02, BA276) and one with low (BA336) pro-inflammatory activity were selected for chemotherapeutic tests in THP-1 cells. All analyzed strains were susceptible to amphotericin B (AmB) but displayed various responses against miltefosine (MIL) and glucantime (GLU). The GV02 strain (canine visceral leishmaniasis) had the highest IC50 for MIL (3.34 mu M), whereas diffuse leishmaniasis strains (BA276 and BA336) had a higher IC50 for GLU (6.87-12.19 mM). The highest IC50 against MIL shown by the GV02 strain has an impact on clinical management. Miltefosine is the only drug approved for dog treatment in Brazil. Further studies into drug susceptibility of L. amazonensis strains are warranted, especially in areas where dog infection by this species overlaps with those caused by Leishmania infantum. (AU)

FAPESP's process: 20/05388-0 - Qualitative and quantitative study of the extracellular matrix (MEC) and immunohistochemical study of subpopulations of skin macrophages in patients with American cutaneous Leishmaniasis (ATL) and Hansen's disease
Grantee:Marcia Dalastra Laurenti
Support Opportunities: Regular Research Grants
FAPESP's process: 21/01243-0 - Biochemical and functional studies of glycoconjugates (LPGs / GIPLs) and prospection of LRV virus in rare dermotropic species/strains of Leishmania.
Grantee:Marcia Dalastra Laurenti
Support Opportunities: Research Grants - Visiting Researcher Grant - Brazil