Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis

Natural killer (NK) cells are bone marrow (BM)-derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection...

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Bibliographic Details
Published in:The Journal of experimental medicine 2012-03, Vol.209 (3), p.565-580
Main Authors: Jaeger, Baptiste N, Donadieu, Jean, Cognet, Céline, Bernat, Claire, Ordoñez-Rueda, Diana, Barlogis, Vincent, Mahlaoui, Nizar, Fenis, Aurore, Narni-Mancinelli, Emilie, Beaupain, Blandine, Bellanné-Chantelot, Christine, Bajénoff, Marc, Malissen, Bernard, Malissen, Marie, Vivier, Eric, Ugolini, Sophie
Format: Article
Language:English
Subjects:
Adult
Animals
Autoimmune Diseases - immunology
Autoimmune Diseases - pathology
Case-Control Studies
Cell Differentiation
Child
Child, Preschool
Female
Homeostasis
Humans
Immunity, Innate
Immunology
Infant
Killer Cells, Natural - immunology
Killer Cells, Natural - pathology
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Transgenic
Middle Aged
Neutropenia - congenital
Neutropenia - immunology
Neutropenia - pathology
Neutrophils - immunology
Neutrophils - pathology
Young Adult
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Summary:Natural killer (NK) cells are bone marrow (BM)-derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection of this phenotype showed that mature neutrophils were required both in the BM and in the periphery for proper NK cell development. In mice lacking neutrophils, NK cells displayed hyperproliferation and poor survival and were blocked at an immature stage associated with hyporesponsiveness. The role of neutrophils as key regulators of NK cell functions was confirmed in patients with severe congenital neutropenia and autoimmune neutropenia. In addition to their direct antimicrobial activity, mature neutrophils are thus endowed with immunoregulatory functions that are conserved across species. These findings reveal novel types of cooperation between cells of the innate immune system and prompt examination of NK cell functional deficiency in patients suffering from neutropenia-associated diseases.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20111908