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Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions.
Front Immunol. 2018; 9:3040.FI

Abstract

Leishmania (Viannia) panamensis (L. (V.) p.) is the main causative agent of cutaneous leishmaniasis in Colombia and is usually treated with either meglumine antimoniate (MA) or miltefosine (MIL). In recent years, there has been increasing evidence of the emergence of drug-resistance against these compounds. Neutrophils are known to play an important role in immunity against Leishmania. These cells are rapidly recruited upon infection and are also present in chronic lesions. However, their involvement in the outcome of infection with drug-resistant Leishmania has not been examined. In this study, human and murine neutrophils were infected in vitro with MA or MIL drug-resistant L. (V.) p. lines derived from a parental L. (V.) p. drug-susceptible strain. Neutrophil effector functions were assessed analyzing the production of reactive oxygen species (ROS), the formation of neutrophil extracellular trap (NET) and the expression of cell surface activation markers. Parasite killing by neutrophils was assessed using L. (V.) p. transfected with a luciferase reporter. We show here that MA and MIL-resistant L. (V.) p. lines elicited significantly increased NET formation and MA-resistant L. (V.) p. induced significantly increased ROS production in both murine and human neutrophils, compared to infections with the parental MIL and MA susceptible strain. Furthermore, neutrophils exposed to drug-resistant lines showed increased activation, as revealed by decreased expression of CD62L and increased expression of CD66b in human neutrophils yet presented higher survival within neutrophils than the drug-susceptible strain. These results provide evidence that parasite drug-susceptibility may influences neutrophil activation and function as well as parasite survival within neutrophils. Further investigaton of the inter-relationship of drug susceptibility and neutrophil effector function should contribute to better understanding of the factors involved in susceptibility to anti-Leishmania drugs.

Authors+Show Affiliations

Department of Biochemistry, WHO-Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.Centro Internacional de Entrenamiento e Investigaciones Médicas, Cali, Colombia. CIDEIM, Universidad ICESI, Cali, Colombia.Department of Biochemistry, WHO-Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.Centro Internacional de Entrenamiento e Investigaciones Médicas, Cali, Colombia. CIDEIM, Universidad ICESI, Cali, Colombia.Centro Internacional de Entrenamiento e Investigaciones Médicas, Cali, Colombia. CIDEIM, Universidad ICESI, Cali, Colombia.Department of Biochemistry, WHO-Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30622537

Citation

Regli, Ivo B., et al. "Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions." Frontiers in Immunology, vol. 9, 2018, p. 3040.
Regli IB, Fernández OL, Martínez-Salazar B, et al. Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions. Front Immunol. 2018;9:3040.
Regli, I. B., Fernández, O. L., Martínez-Salazar, B., Gómez, M. A., Saravia, N. G., & Tacchini-Cottier, F. (2018). Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions. Frontiers in Immunology, 9, 3040. https://doi.org/10.3389/fimmu.2018.03040
Regli IB, et al. Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions. Front Immunol. 2018;9:3040. PubMed PMID: 30622537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions. AU - Regli,Ivo B, AU - Fernández,Olga Lucía, AU - Martínez-Salazar,Berenice, AU - Gómez,Maria Adelaida, AU - Saravia,Nancy Gore, AU - Tacchini-Cottier,Fabienne, Y1 - 2018/12/21/ PY - 2018/09/14/received PY - 2018/12/10/accepted PY - 2019/1/10/entrez PY - 2019/1/10/pubmed PY - 2019/10/28/medline KW - Leishmania KW - NETs KW - antimony KW - drug resistance KW - miltefosine KW - neutrophils SP - 3040 EP - 3040 JF - Frontiers in immunology JO - Front Immunol VL - 9 N2 - Leishmania (Viannia) panamensis (L. (V.) p.) is the main causative agent of cutaneous leishmaniasis in Colombia and is usually treated with either meglumine antimoniate (MA) or miltefosine (MIL). In recent years, there has been increasing evidence of the emergence of drug-resistance against these compounds. Neutrophils are known to play an important role in immunity against Leishmania. These cells are rapidly recruited upon infection and are also present in chronic lesions. However, their involvement in the outcome of infection with drug-resistant Leishmania has not been examined. In this study, human and murine neutrophils were infected in vitro with MA or MIL drug-resistant L. (V.) p. lines derived from a parental L. (V.) p. drug-susceptible strain. Neutrophil effector functions were assessed analyzing the production of reactive oxygen species (ROS), the formation of neutrophil extracellular trap (NET) and the expression of cell surface activation markers. Parasite killing by neutrophils was assessed using L. (V.) p. transfected with a luciferase reporter. We show here that MA and MIL-resistant L. (V.) p. lines elicited significantly increased NET formation and MA-resistant L. (V.) p. induced significantly increased ROS production in both murine and human neutrophils, compared to infections with the parental MIL and MA susceptible strain. Furthermore, neutrophils exposed to drug-resistant lines showed increased activation, as revealed by decreased expression of CD62L and increased expression of CD66b in human neutrophils yet presented higher survival within neutrophils than the drug-susceptible strain. These results provide evidence that parasite drug-susceptibility may influences neutrophil activation and function as well as parasite survival within neutrophils. Further investigaton of the inter-relationship of drug susceptibility and neutrophil effector function should contribute to better understanding of the factors involved in susceptibility to anti-Leishmania drugs. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/30622537/Resistance_of_Leishmania__Viannia__Panamensis_to_Meglumine_Antimoniate_or_Miltefosine_Modulates_Neutrophil_Effector_Functions_ L2 - https://doi.org/10.3389/fimmu.2018.03040 DB - PRIME DP - Unbound Medicine ER -