title: Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice.
abstract: Systemic inflammatory response syndrome is a whole-body reaction to a triggering insult that often results in life-threatening illness. Contributing to the development of this inflammatory cascade are numerous cellular partners, among which NK cells were shown to play a key role. Accumulating evidence points to organ-specific properties of systemic inflammation and NK cells. However, little is known about compartment-specific activation of NK cells during systemic inflammatory response syndrome or the relative contribution of NK cell-intrinsic properties and microenvironmental cues. In this study, we undertook a sequential characterization of NK responses in the spleen, lungs, bone marrow, peritoneum, and blood using a mouse model of endotoxemia. We report that, despite similar systemic dynamics of NK cell responses, expression of activation markers (CD69 and CD25) and effector molecules (IFN-γ, granzyme B, and IL-10) display organ-specific thresholds of maximum activation. Using adoptive transfers of spleen and lung NK cells, we found that these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. This functional adaptation occurs without significant alterations in phenotype and independently of subpopulation-specific trafficking. Thus, using a dynamic in vivo-transfer system, to our knowledge our study is the first to report the compartmentalization of NK cells responses during systemic inflammation and to show that NK cell-intrinsic properties and microenvironmental cues are involved in this process, in a sequential manner.
authors: Unité Cytokines & Inflammation, Département Infection et Epidémiologie, Institut Pasteur, 75015 Paris, France; and orhan.rasid@pasteur.fr jean-marc.cavaillon@pasteur.fr.
authors: Orhan
authors: O
authors: Rasid
authors: Unité Cytokines & Inflammation, Département Infection et Epidémiologie, Institut Pasteur, 75015 Paris, France; and Cantacuzino National Research Institute, 050096 Bucharest, Romania.
authors: Ioana Sonya
authors: 0000-0002-5102-1026
authors: IS
authors: Ciulean
authors: Unité Cytokines & Inflammation, Département Infection et Epidémiologie, Institut Pasteur, 75015 Paris, France; and.
authors: Catherine
authors: 0000-0002-5420-8400
authors: C
authors: Fitting
authors: Unité Cytokines & Inflammation, Département Infection et Epidémiologie, Institut Pasteur, 75015 Paris, France; and.
authors: Noelle
authors: N
authors: Doyen
authors: Unité Cytokines & Inflammation, Département Infection et Epidémiologie, Institut Pasteur, 75015 Paris, France; and orhan.rasid@pasteur.fr jean-marc.cavaillon@pasteur.fr.
authors: Jean-Marc
authors: JM
authors: Cavaillon
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D060833:Cellular Microenvironment; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053804:Granzymes; D007371:Interferon-gamma; D016753:Interleukin-10; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D000099192:CD69 Antigens