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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3614-3615.
Control LPS or get killedTHE HEBREW UNIVERSITY
In this issue of Blood, Nedvetzki and colleagues demonstrate functional crosstalk between NK cells and macrophages; the outcome of these interactions is dependent on the extent of LPS stimulation.
Nedvetzki and colleagues, in the current issue of Blood, further extend the possible immune-regulatory role of human NK cells by examining their interactions with macrophages. They show, using a series of elegant experiments, that macrophages, via the engagement of 2B4, activate NK-cell proliferation and cytokine secretion and increase NK-cell cytotoxicity against susceptible target cells. On the other hand, the authors demonstrate that NK cells control macrophage activity, by NKG2D-dependent killing of macrophages stimulated by high doses of LPS. In this regard, it will be interesting to test whether other TLR stimulations will induce human NKG2D ligand expression and, consequently, killing by NK cells. Finally, using macrophages or macrophages stimulated with LPS, the authors demonstrate that the distinct functions of NK-cell–macrophage interactions are translated into different structures of immune synapses (see figure).
Nedvetzki and colleagues demonstrate functional interactions between NK cells and macrophages. Where, in vivo, could such interactions occur? One possible place is the site of inflammation, where cytokines and chemokines produced by resident macrophages or other cell types could attract NK cells. In such a case, the interactions between NK cells and macrophages could prime NK-cell effector functions in the inflamed tissue. It is also possible that macrophages play a role in recruiting NK cells to lymph nodes, as previously demonstrated for DCs.2 Developing in vivo techniques to image NK-cell–macrophage interaction will probably lead to a better understanding of the importance of NK-cell–macrophage crosstalk. Another issue to consider is when macrophages need to be killed. It is tempting to speculate that NK-cell–mediated killing of macrophages is important during chronic inflammatory reaction when the macrophage activity needs to be stopped, to prevent, for example, septic shock. The macrophage-mediated killing by NK cells might also be important in eliminating macrophages infected with pathogens such as Mycobacterium tuberculosis. In those situations, LPS-induced expression of NK-cell–activating ligands may aid in the elimination of macrophages exposed to, or infected by, the pathogens. Finally, several reports have recently demonstrated that NK cells, themselves, might also serve as antigen-presenting cells (APCs).3 These observations, together with the results of Nedvetzki and colleagues and the accumulating evidence demonstrating interactions between NK cells and DCs,4 suggest a possible APC network communication. Such a communication might be used, for example, to transfer peptides from one APC to another, for presentation to T cells. It will be interesting to test whether B cells, which can also serve as APCs, might directly interact with NK cells.
Footnotes
Conflict-of-interest disclosure: The authors declare no competing financial interests.
REFERENCES
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
