Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection.
Local production of IL-17 is a significant factor in effective host defense against Gram-negative bacteria. However, the proximal events mediating IL-17 elaboration by T cells remain unclear. In this study, we show in vivo that intact Toll-like receptor 4 signaling in the lung is required for induction of both the p19 transcript of IL-23 and IL-17 protein elaboration in response to Klebsiella pneumoniae. Although IL-17 is widely considered a CD4(+) T cell product, we also demonstrate significant in vitro IL-17 production by CD8(+) T cells after culture in medium from dendritic cells exposed to these bacteria. The dominant portion of this IL-17-inducing activity for both CD4(+) and CD8(+) T cells is IL-23. These data demonstrate the critical signaling pathway for IL-17 induction in the host response to Gram-negative pulmonary infection and suggest a direct role for IL-23 in CD8(+) T cell IL-17 production.
Happel
Kyle I
KI
Section of Pulmonary and Critical Care Medicine, Alcohol Research Center, Gene Therapy Program, and Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
Zheng
Mingquan
M
Young
Erana
E
Quinton
Lee J
LJ
Lockhart
Euan
E
Ramsay
Alistair J
AJ
Shellito
Judd E
JE
Schurr
Jill R
JR
Bagby
Gregory J
GJ
Nelson
Steve
S
Kolls
Jay K
JK
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics / Q000502:physiology*; D007710:Klebsiella Infections / Q000276:immunology* / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors
C508841:Il23a protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors