Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis.
The importance of T helper type 1 (Th1) cell immunity in host resistance to the intracellular bacterium Francisella tularensis is well established. However, the relative roles of interleukin (IL)-12-Th1 and IL-23-Th17 cell responses in immunity to F. tularensis have not been studied. The IL-23-Th17 cell pathway is critical for protective immunity against extracellular bacterial infections. In contrast, the IL-23-Th17 cell pathway is dispensable for protection against intracellular pathogens such as Mycobacteria. Here we show that the IL-23-Th17 pathway regulates the IL-12-Th1 cell pathway and was required for protective immunity against F.tularensis live vaccine strain. We show that IL-17A, but not IL-17F or IL-22, induced IL-12 production in dendritic cells and mediated Th1 responses. Furthermore, we show that IL-17A also induced IL-12 and interferon-gamma production in macrophages and mediated bacterial killing. Together, these findings illustrate a biological function for IL-17A in regulating IL-12-Th1 cell immunity and host responses to an intracellular pathogen.
Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Yinyao
Y
Lin
Shane
S
Ritchea
Alison
A
Logar
Samantha
S
Slight
Michelle
M
Messmer
Javier
J
Rangel-Moreno
Lokesh
L
Guglani
John F
JF
Alcorn
Heather
H
Strawbridge
Sang Mi
SM
Park
Reiko
R
Onishi
Nikki
N
Nyugen
Michael J
MJ
Walter
Derek
D
Pociask
Troy D
TD
Randall
Sarah L
SL
Gaffen
Yoichiro
Y
Iwakura
Jay K
JK
Kolls
Shabaana A
SA
Khader
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D005604:Francisella tularensis / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D014406:Tularemia / Q000276:immunology* / Q000517:prevention & control*
D020381:Interleukin-17; D053759:Interleukin-23; D007371:Interferon-gamma