Immuno-metabolic profile of human macrophages after Leishmania and Trypanosoma cruzi infection
Ty, M. C. (New York University School of Medicine. Department of Microbiology)
Loke, P. (New York University School of Medicine. Department of Microbiology)
Alberola, Jordi (Alberola i Domingo) (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Rodriguez-Cortes, Alheli (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)

Data:	2019
Resum:	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.
Nota:	This work was by funded by the NIH/NIAID training grant: 5T32AI007180 to MCT. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Nota:	Altres ajuts: NIH/NIAID/5T32AI007180
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	3T3 Cells ; Animals ; Cells, Cultured ; Chagas Disease ; Cytokines ; Healthy Volunteers ; Humans ; Leishmania donovani ; Leishmania mexicana ; Leishmaniasis ; Macrophage Activation ; Macrophages ; Metabolome ; Mice ; Oxidative Phosphorylation ; Primary Cell Culture ; Trypanosoma cruzi ; Up-Regulation
Publicat a:	PloS one, Vol. 14 Núm. 12 (december 2019) , p. e0225588, ISSN 1932-6203

DOI: 10.1371/journal.pone.0225588
PMID: 31841511

12 p, 1.6 MB

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