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Immuno-metabolic profile of human macrophages after Leishmania and Trypanosoma cruzi infection


Autoři: Maureen C. Ty aff001;  P’ng Loke aff001;  Jordi Alberola aff002;  Ana Rodriguez aff001;  Alheli Rodriguez-Cortes aff001
Působiště autorů: New York University School of Medicine, Department of Microbiology, New York, NY, United States of America aff001;  Dept Farmacologia, Toxicologia i Terapeutica, Facultat de Veterinaria, Edifici V, Universitat Autonoma de Barcelona, Bellaterra, Spain aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225588

Souhrn

Macrophages can reprogram their metabolism in response to the surrounding stimuli, which affects their capacity to kill intracellular pathogens. We have investigated the metabolic and immune status of human macrophages after infection with the intracellular trypanosomatid parasites Leishmania donovani, L. amazonensis and T. cruzi and their capacity to respond to a classical polarizing stimulus (LPS and IFN-γ). We found that macrophages infected with Leishmania preferentially upregulate oxidative phosphorylation, which could be contributed by both host cell and parasite, while T. cruzi infection did not significantly increase glycolysis or oxidative phosphorylation. Leishmania and T. cruzi infect macrophages without triggering a strong inflammatory cytokine response, but infection does not prevent a potent response to LPS and IFN-γ. Infection appears to prime macrophages, since the cytokine response to activation with LPS and IFN-γ is more intense in infected macrophages compared to uninfected ones. Metabolic polarization in macrophages can influence infection and immune evasion of these parasites since preventing macrophage cytokine responses would help parasites to establish a persistent infection. However, macrophages remain responsive to classical inflammatory stimuli and could still trigger inflammatory cytokine secretion by macrophages.

Klíčová slova:

Cytokines – Inflammation – Respiratory infections – Parasitic diseases – Glycolysis – Macrophages – Trypanosoma cruzi – Leishmania donovani


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