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Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems

BACKGROUND: Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocyte...

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Autores principales: Stinchcombe, Jane C, Salio, Mariolina, Cerundolo, Vincenzo, Pende, Daniela, Arico, Maurizo, Griffiths, Gillian M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149597/
https://www.ncbi.nlm.nih.gov/pubmed/21711522
http://dx.doi.org/10.1186/1741-7007-9-45
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author Stinchcombe, Jane C
Salio, Mariolina
Cerundolo, Vincenzo
Pende, Daniela
Arico, Maurizo
Griffiths, Gillian M
author_facet Stinchcombe, Jane C
Salio, Mariolina
Cerundolo, Vincenzo
Pende, Daniela
Arico, Maurizo
Griffiths, Gillian M
author_sort Stinchcombe, Jane C
collection PubMed
description BACKGROUND: Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. RESULTS: NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked') with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. CONCLUSIONS: These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system) direct secretory lysosomes to the immunological synapse. Morphologically, the overall structure of the immunological synapses formed by NK and iNKT cells are very similar to those formed by CTLs, with both exocytic and endocytic organelles polarised towards the centrosome at the plasma membrane, which forms a focal point for exocytosis and endocytosis within the immunological synapse. We conclude that centrosomal polarisation provides a rapid, responsive and precise mechanism for secretory lysosome delivery to the immunological synapse in CTLs, NK cells and iNKT cells.
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spelling pubmed-31495972011-08-04 Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems Stinchcombe, Jane C Salio, Mariolina Cerundolo, Vincenzo Pende, Daniela Arico, Maurizo Griffiths, Gillian M BMC Biol Research Article BACKGROUND: Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. RESULTS: NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked') with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. CONCLUSIONS: These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system) direct secretory lysosomes to the immunological synapse. Morphologically, the overall structure of the immunological synapses formed by NK and iNKT cells are very similar to those formed by CTLs, with both exocytic and endocytic organelles polarised towards the centrosome at the plasma membrane, which forms a focal point for exocytosis and endocytosis within the immunological synapse. We conclude that centrosomal polarisation provides a rapid, responsive and precise mechanism for secretory lysosome delivery to the immunological synapse in CTLs, NK cells and iNKT cells. BioMed Central 2011-06-28 /pmc/articles/PMC3149597/ /pubmed/21711522 http://dx.doi.org/10.1186/1741-7007-9-45 Text en Copyright ©2011 Stinchcombe et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Stinchcombe, Jane C
Salio, Mariolina
Cerundolo, Vincenzo
Pende, Daniela
Arico, Maurizo
Griffiths, Gillian M
Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems
title Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems
title_full Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems
title_fullStr Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems
title_full_unstemmed Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems
title_short Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems
title_sort centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149597/
https://www.ncbi.nlm.nih.gov/pubmed/21711522
http://dx.doi.org/10.1186/1741-7007-9-45
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