Re-organization of mitochondria at the NK cell immune synapse.
As part of the innate immune response NK cells destroy infected, transformed, or otherwise stressed cells within hours of activation. In contrast, CD4(+) T lymphocytes require a sustained increase in their metabolism in order to cope with the biogenesis of cell components, in a process of proliferation and differentiation into effector cells. Recently, mitochondria have been implied in T lymphocyte immune synapse function but little is known on the role of mitochondria in the NK cell interaction with tumour cells. Here we analysed NK cells mitochondrial membrane potential (Deltapsi(m)) as an indicator of mitochondrial energy status and cellular homeostasis. Upon contact with K562 tumour cells, NK cells undergo Deltapsi(m) depolarization, indicating a rapid consumption of their metabolic energy. Furthermore, pharmacological inhibition of ATP synthesis down-regulates NK cell cytotoxic activity. Confocal- and electron-microscopy analyses showed re-organization of NK cells mitochondria towards the site of interaction with K562 tumour cell (NK cell immune synapse), perhaps as a way to compensate for local energy consumption. Interestingly, mitochondrial re-organization also takes place following NK stimulation with anti-NKGD2 antibodies but not with anti-KIR2DL1 antibodies, suggesting that activating rather than inhibiting cell signalling, triggered by NK cell receptors, is involved in NK cell mitochondria dynamics.
Abarca-Rojano
Edgar
E
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politecnico Nacional, Carpio y Plan de Ayala, México, Mexico.
Muñiz-Hernández
Saé
S
Moreno-Altamirano
María Maximina Bertha
MM
Mondragón-Flores
Ricardo
R
Enriquez-Rincón
Fernando
F
Sánchez-García
F Javier
FJ
D000911:Antibodies, Monoclonal; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D054992:Immunological Synapses / Q000378:metabolism*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000276:immunology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009840:Oligomycins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009840:Oligomycins; D025261:Mitochondrial Proton-Translocating ATPases