Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis

Yinyao Lin; Shane Ritchea; Alison Logar; Samantha Slight; Michelle Messmer; Javier Rangel-Moreno; Lokesh Guglani; John F. Alcorn; Heather Strawbridge; Sang Mi Park; Reiko Onishi; Nikki Nyugen; Michael J. Walter; Derek Pociask; Troy D. Randall; Sarah L. Gaffen; Yoichiro Iwakura; Jay K. Kolls; Shabaana A. Khader

doi:10.1016/j.immuni.2009.08.025

Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis

Yinyao Lin, Shane Ritchea, Alison Logar, Samantha Slight, Michelle Messmer, Javier Rangel-Moreno, Lokesh Guglani, John F. Alcorn, Heather Strawbridge, Sang Mi Park, Reiko Onishi, Nikki Nyugen, Michael J. Walter, Derek Pociask, Troy D. Randall, Sarah L. Gaffen, Yoichiro Iwakura, Jay K. Kolls, Shabaana A. Khader

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Abstract

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-γ 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.

Original language	English
Pages (from-to)	799-810
Number of pages	12
Journal	Immunity
Volume	31
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2009.08.025
State	Published - Nov 20 2009

Keywords

CELLIMMUNO
MOLIMMUNO

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Lin, Y., Ritchea, S., Logar, A., Slight, S., Messmer, M., Rangel-Moreno, J., Guglani, L., Alcorn, J. F., Strawbridge, H., Park, S. M., Onishi, R., Nyugen, N., Walter, M. J., Pociask, D., Randall, T. D., Gaffen, S. L., Iwakura, Y., Kolls, J. K., & Khader, S. A. (2009). Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis. Immunity, 31(5), 799-810. https://doi.org/10.1016/j.immuni.2009.08.025

@article{16fcf92c6ee1433da71fba47c7bce6f0,

title = "Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis",

abstract = "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-γ 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.",

keywords = "CELLIMMUNO, MOLIMMUNO",

author = "Yinyao Lin and Shane Ritchea and Alison Logar and Samantha Slight and Michelle Messmer and Javier Rangel-Moreno and Lokesh Guglani and Alcorn, {John F.} and Heather Strawbridge and Park, {Sang Mi} and Reiko Onishi and Nikki Nyugen and Walter, {Michael J.} and Derek Pociask and Randall, {Troy D.} and Gaffen, {Sarah L.} and Yoichiro Iwakura and Kolls, {Jay K.} and Khader, {Shabaana A.}",

note = "Funding Information: This work was supported by Children's Hospital Of Pittsburgh and AI075106 to S.A.K., HL69409 to T.D.R., and AR054389 to S.L.G. The authors thank L. Bauer and A. Magill for technical help and G. Kirimanjeswara and D. Metzger, Albany Medical College, for F. tularensis LVS infection protocols. They also thank N. Ghilardi and O. Wenjun, Genentech Inc., for providing Il23a −/− and Il22 −/− mice, respectively. Il17ra −/− mice were a kind gift from Amgen Inc. The authors thank J. Piganelli for critical reading of the manuscript. S.L.G. has received travel reimbursement, honoraria, and a research grant from Amgen Inc. ",

year = "2009",

month = nov,

day = "20",

doi = "10.1016/j.immuni.2009.08.025",

language = "English",

volume = "31",

pages = "799--810",

journal = "Immunity",

issn = "1074-7613",

number = "5",

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Lin, Y, Ritchea, S, Logar, A, Slight, S, Messmer, M, Rangel-Moreno, J, Guglani, L, Alcorn, JF, Strawbridge, H, Park, SM, Onishi, R, Nyugen, N, Walter, MJ, Pociask, D, Randall, TD, Gaffen, SL, Iwakura, Y, Kolls, JK & Khader, SA 2009, 'Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis', Immunity, vol. 31, no. 5, pp. 799-810. https://doi.org/10.1016/j.immuni.2009.08.025

TY - JOUR

T1 - Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis

AU - Lin, Yinyao

AU - Ritchea, Shane

AU - Logar, Alison

AU - Slight, Samantha

AU - Messmer, Michelle

AU - Rangel-Moreno, Javier

AU - Guglani, Lokesh

AU - Alcorn, John F.

AU - Strawbridge, Heather

AU - Park, Sang Mi

AU - Onishi, Reiko

AU - Nyugen, Nikki

AU - Walter, Michael J.

AU - Pociask, Derek

AU - Randall, Troy D.

AU - Gaffen, Sarah L.

AU - Iwakura, Yoichiro

AU - Kolls, Jay K.

AU - Khader, Shabaana A.

N1 - Funding Information: This work was supported by Children's Hospital Of Pittsburgh and AI075106 to S.A.K., HL69409 to T.D.R., and AR054389 to S.L.G. The authors thank L. Bauer and A. Magill for technical help and G. Kirimanjeswara and D. Metzger, Albany Medical College, for F. tularensis LVS infection protocols. They also thank N. Ghilardi and O. Wenjun, Genentech Inc., for providing Il23a −/− and Il22 −/− mice, respectively. Il17ra −/− mice were a kind gift from Amgen Inc. The authors thank J. Piganelli for critical reading of the manuscript. S.L.G. has received travel reimbursement, honoraria, and a research grant from Amgen Inc.

PY - 2009/11/20

Y1 - 2009/11/20

N2 - 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-γ 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.

AB - 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-γ 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.

KW - CELLIMMUNO

KW - MOLIMMUNO

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U2 - 10.1016/j.immuni.2009.08.025

DO - 10.1016/j.immuni.2009.08.025

M3 - Article

C2 - 19853481

AN - SCOPUS:70449501815

SN - 1074-7613

VL - 31

SP - 799

EP - 810

JO - Immunity

JF - Immunity

IS - 5

ER -

Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis

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