Mouse Lung and Spleen Natural Killer Cells Have Phenotypic and Functional Differences, in Part Influenced by Macrophages

Abstract

NK cells are lymphocytes of the innate immune system which are a first line of defense against infections and tumor cells, in bone marrow and peripheral organs like lung and spleen. The lung is an organ in contact with respiratory pathogens and the site of inflammatory disorders triggered by the respiratory environment. In contrast, spleen is a lymphatic organ connected to the blood system which regulates the systemic immune response. Here we compare NK cell maturation and expansion as well as expression of NK cell receptors in spleen and lung compartments. We show that spleen and lung NK cells differ in phenotypic and functional characteristics due to a difference of maturity and cellular microenvironment. Indeed we observe that spleen and lung macrophages have the capacity to influence the cytotoxicity of NK cells by cell-to-cell contact. This suggests that the differences of NK cell subsets are in part due to a modulation by the organ environment.

Conditional ablation of NKp46+ cells using a novel Ncr1greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

“…In humans and mice, primary melanomas as well as melanoma derived cell lines have been shown to express ligands for NKp46 and DNAM1 explaining their susceptibility to NK-cell mediated lysis [39]. However, more recent data suggest that the ability of NK cells to lyse B16 cells might differ depending on the tissue of origin of the effector cells [42]. This might in part be due to differences in accessory cells within tissues [42,43].…”

“…However, more recent data suggest that the ability of NK cells to lyse B16 cells might differ depending on the tissue of origin of the effector cells [42]. This might in part be due to differences in accessory cells within tissues [42,43]. Experimental procedures aiming at the study of NK cells usually either involve the depletion of NK cells using monoclonal antibodies, like anti-NK1.1 or anti-asialo-GM1, both of which are not NK-cell-specific but deplete also subsets of T cells, or the use of immune-deficient mice, like Rag2 −/− γc −/− mice that lack not only NK cells, but also other ILC lineages as well as B and T cells, and display defects in lymphoid tissues, like lymph nodes and Peyer's patches [44].…”

Consequences of the crosstalk between monocytes/macrophages and natural killer cells

“…Mouse NK cells from lung and spleen are quite different and react differently in contact with spleen or lung macrophages. Spleen macrophages have the tendency to induce a stronger activation of NK cell cytotoxicity than lung macrophages (Michel et al, 2012). Furthermore, depending on the tissue environment, human macrophages are polarized toward either M1 or M2 subsets which display different functionality (Biswas and Mantovani, 2010).…”

Recombinant Ehrlichia P29 protein induces a protective immune response in a mouse model of ehrlichiosis

“…However, immunization with rP29 reduced the bacterial burden in only some of the organs examined following high dose challenge infection compared to E. muris -immune mice. The reasons for the observed differences in protection against the high dose challenge infection in different organs of mice immunized with rP29 are not known, and these could be due to differences in the bacterial burdens or due to differences in the number and composition of the cells of the immune system and their functional heterogeneity in different organs [39–41]. The data suggested that immunity generated by natural E. muris infection is superior to protection induced by rP29.…”