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Interaction of Mycobacterium tuberculosis Cell Wall Components with the Human Natural Killer Cell Receptors NK p44 and Toll‐Like Receptor 2
Author(s) -
Esin S.,
Counoupas C.,
Aulicino A.,
Brancatisano F. L.,
Maisetta G.,
Bottai D.,
Luca M.,
Florio W.,
Campa M.,
Batoni G.
Publication year - 2013
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12052
Subject(s) - tlr2 , peptidoglycan , mycobacterium tuberculosis , cell wall , receptor , chemistry , microbiology and biotechnology , natural killer cell , cell , biology , cytotoxicity , innate immune system , tuberculosis , biochemistry , in vitro , medicine , pathology
We have previously demonstrated that a soluble form of the human NK cell natural cytotoxicity receptor NK p44, binds to the surface of M ycobacterium tuberculosis ( MTB ). Herein, we investigated the interaction of MTB cell wall components ( CWC ) with NK p44 or with T oll‐like receptor 2 ( TLR 2) and the role of NK p44 and TLR 2 in the direct activation of NK cells upon stimulation with MTB CWC . By using several purified bacterial CWC in an ELISA , we demonstrated that NK p44 was able to bind to the MTB cell wall core mycolyl‐arabinogalactan‐peptidoglycan ( mAGP ) as well as to mycolic acids ( MA ) and arabinogalactan ( AG ), while soluble TLR 2 bound to MTB peptidoglycan ( PG ), but not to MA or AG . The mAGP complex induced NK cell expression of CD 25, CD 69, NK p44 and IFN ‐γ production at levels comparable to M . bovis B acillus C almette– G uérin‐stimulated ( BCG ) cells. While AG and MA used alone failed to induce NK cell activation, mycobacterial PG ‐exhibited NK cell stimulatory capacity. Activation of resting NK cells by mAGP and IFN ‐γ production were inhibited by anti‐ TLR 2 MA b, but not by anti‐ NK p44 MA b. Differently, anti‐ NK p44 MA b partially inhibited CD 69 expression on NK cells pre‐activated with IL ‐2 and then stimulated with mAGP or whole BCG . Overall, these results provide evidence that components abundant in mycobacterial cell wall are able to interact with NK p44 ( AG , MA ) and TLR ‐2 ( PG ), respectively. While interaction of TLR 2 with mycobacterial cell wall promotes activation of resting NK cells and IFN ‐γ production, NK p44 interaction with its putative ligands could play a secondary role in maintaining cell activation.