IL-22 produced by human NK cells inhibits growth of Mycobacterium tuberculosis by enhancing phagolysosomal fusion.
We determined whether human NK cells could contribute to immune defenses against Mycobacterium tuberculosis through production of IL-22. CD3(-)CD56(+) NK cells produced IL-22 when exposed to autologous monocytes and gamma-irradiated M. tuberculosis, and this depended on the presence of IL-15 and IL-23, but not IL-12 or IL-18. IL-15-stimulated NK cells expressed 10.6 times more DAP10 mRNA compared with control NK cells, and DAP10 siRNA inhibited IL-15-mediated IL-22 production by NK cells. Soluble factors produced by IL-15-activated NK cells inhibited growth of M. tuberculosis in macrophages, and this effect was reversed by anti-IL-22. Addition of rIL-22 to infected macrophages enhanced phagolysosomal fusion and reduced growth of M. tuberculosis. We conclude that NK cells can contribute to immune defenses against M. tuberculosis through production of IL-22, which inhibits intracellular mycobacterial growth by enhancing phagolysosomal fusion. IL-15 and DAP-10 elicit IL-22 production by NK cells in response to M. tuberculosis.
Center for Pulmonary and Infectious Disease Control, Department of Microbiology and Immunology, University of Texas Health Center, Tyler, TX 75708-3154, USA.
Rohan
R
Dhiman
Mohanalaxmi
M
Indramohan
Peter F
PF
Barnes
Ramesh C
RC
Nayak
Padmaja
P
Paidipally
L Vijaya Mohan
LV
Rao
Ramakrishna
R
Vankayalapati
D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D053759:Interleukin-23 / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D010588:Phagosomes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D012333:RNA, Messenger / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000819:agonists / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D000097043:Interleukin-22
D018664:Interleukin-12; D019409:Interleukin-15; D020382:Interleukin-18; D053759:Interleukin-23; D007378:Interleukins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D000097043:Interleukin-22; C120528:HCST protein, human