IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge

Shabaana A. Khader, Guy K. Bell, John E. Pearl, Jeffrey J. Fountain, Javier Rangel-Moreno, Garth E. Cilley, Fang Shen, Sheri M. Eaton, Sarah L. Gaffen, Susan L. Swain, Richard M. Locksley, Laura Haynes, Troy D. Randall, Andrea M. Cooper

Research output: Contribution to journalArticlepeer-review

1092 Scopus citations

Abstract

Interferon-γ is key in limiting Mycobacterium tuberculosis infection. Here we show that vaccination triggered an accelerated interferon-γ response by CD4+ T cells in the lung during subsequent M. tuberculosis infection. Interleukin 23 (IL-23) was essential for the accelerated response, for early cessation of bacterial growth and for establishment of an IL-17-producing CD4+ T cell population in the lung. The recall response of the IL-17-producing CD4+ T cell population occurred concurrently with expression of the chemokines CXCL9, CXCL10 and CXCL11. Depletion of IL-17 during challenge reduced the chemokine expression and accumulation of CD4+ T cells producing interferon-gamma; in the lung. We propose that vaccination induces IL-17-producing CD4+ T cells that populate the lung and, after challenge, trigger the production of chemokines that recruit CD4+ T cells producing interferon-γ, which ultimately restrict bacterial growth.

Original languageEnglish
Pages (from-to)369-377
Number of pages9
JournalNature immunology
Volume8
Issue number4
DOIs
StatePublished - Apr 2007

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