Heterogeneity of TLR3 mRNA transcripts and responsiveness to poly (I:C) in human NK cells derived from different donors.
TLR3 plays an important role in the activation of different cell types of the innate immune system. Previous studies indicated that human NK cells express TLR3 and that, upon stimulation by polyinosinic-polycytidylic acid [poly (I:C)], they release cytokines and up-regulate cytotoxicity. Here we show that NK cells display heterogeneous levels of TLR3 mRNA transcript. Analysis of NK cell clones did not reveal significant correlation between the levels of TLR3 mRNA transcripts and the expression of different surface NK receptors including killer Ig-like receptor and NKG2A. On the other hand, the level of TLR3 mRNA transcript detected in given clones correlated with the ability of these clones to respond to poly (I:C). Thus, clones displaying higher TLR3 mRNA transcripts were characterized by higher cytokine production and cytotoxicity. Moreover, the increased cytolytic activity induced by treatment with poly (I:C) does not depend on increment of the expression of activating NK receptors and co-receptors, adhesion molecules or perforin/granzyme, but correlates with higher cell responsiveness to NKp46 ligation. Remarkably, in the presence of poly (I:C), even NKp46(dull) NK cell clones become cytolytic when characterized by high levels of TLR3 transcript. Thus, our present study provides an useful tool for both a quantitative and qualitative analysis of TLR3 in NK cells and contributes to explain the heterogeneous responsiveness to poly (I:C) of NK cells derived from different individuals.
Sivori
Simona
S
Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy.
Falco
Michela
M
Carlomagno
Simona
S
Romeo
Elisa
E
Moretta
Lorenzo
L
Moretta
Alessandro
A
D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D055627:Natural Cytotoxicity Triggering Receptor 1; D011070:Poly I-C / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; C437968:PLAAT4 protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018168:Receptors, Retinoic Acid; D051196:Toll-Like Receptor 3; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C