IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge.
Interferon-gamma is key in limiting Mycobacterium tuberculosis infection. Here we show that vaccination triggered an accelerated interferon-gamma 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-gamma, which ultimately restrict bacterial growth.
Khader
Shabaana A
SA
Trudeau Institute, Saranac Lake, New York 12983, USA.
Bell
Guy K
GK
Pearl
John E
JE
Fountain
Jeffrey J
JJ
Rangel-Moreno
Javier
J
Cilley
Garth E
GE
Shen
Fang
F
Eaton
Sheri M
SM
Gaffen
Sarah L
SL
Swain
Susan L
SL
Locksley
Richard M
RM
Haynes
Laura
L
Randall
Troy D
TD
Cooper
Andrea M
AM
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D020381:Interleukin-17; D053759:Interleukin-23; D032581:Tuberculosis Vaccines