NKG2D-dependent IL-17 production by human T cells in response to an intracellular pathogen.
We studied the factors that control IL-17 production in human Mycobacterium tuberculosis infection. CD4(+) cells from healthy tuberculin reactors produced IL-17 in response to autologous M. tuberculosis-stimulated monocytes, and most IL-17(+) cells were Ag experienced, CD4(+)CD62L(-). IL-17 production by CD4(+) cells was inhibited by anti-IL-23, but not by Abs to IL-1, IL-6, or TGF-beta. Anti-NKG2D reduced IL-17 production and the frequency of CD4(+)CD62(-) IL-17(+) cells, suggesting that NKG2D stimulates IL-17 production. CD4(+)NKG2D(+) cells did not produce IL-17. Monocytes and alveolar macrophages from healthy donors produced IL-23 in response to M. tuberculosis. Addition of CD4(+) cells markedly enhanced IL-23 production by M. tuberculosis-stimulated monocytes, and this was inhibited by anti-NKG2D and by Abs to UL-16 binding protein (ULB)1, a ligand for NKG2D on APCs. We conclude that binding of NKG2D to UL-16 binding protein (ULB)1 contributes to IL-23-dependent IL-17 production by CD4(+) cells in human M. tuberculosis infection.
Paidipally
Padmaja
P
Departments of Microbiology, University of Texas Health Center, Center for Pulmonary and Infectious Disease Control, Tyler, TX 75708, USA.
Periasamy
Sivakumar
S
Barnes
Peter F
PF
Dhiman
Rohan
R
Indramohan
Mohanalaxmi
M
Griffith
David E
DE
Cosman
David
D
Vankayalapati
Ramakrishna
R
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology*
D000942:Antigens, Bacterial; D058851:GPI-Linked Proteins; D020381:Interleukin-17; D053759:Interleukin-23; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C423231:ULBP1 protein, human