BACKGROUND: Mycobacterium tuberculosis infects one third of the world's population and causes >8 million cases of tuberculosis annually. New vaccines are necessary to control the spread of tuberculosis. T cells, interferon γ (IFN-γ), and tumor necrosis factor (TNF) are necessary to control M. tuberculosis infection in both humans and unvaccinated experimental animal models. However, the immune responses necessary for vaccine efficacy against M. tuberculosis have not been defined. The multifunctional activity of T-helper type 1 (TH1) cells that simultaneously produce IFN-γ and TNF has been proposed as a candidate mechanism of vaccine efficacy. METHODS: We used a mouse model of T-cell transfer and aerosolized M. tuberculosis infection to assess the contributions of TNF, IFN-γ, and inducible nitric oxide synthase (iNOS) to vaccine efficacy. RESULTS: CD4(+) T cells were necessary and sufficient to transfer protection against aerosolized M. tuberculosis, but neither CD4(+) T cell-produced TNF nor host cell responsiveness to IFN-γ were necessary. Transfer of Tnf(-/-) CD4(+) T cells from vaccinated donors to Ifngr(-/-) recipients was also sufficient to confer protection. Activation of iNOS to produce reactive nitrogen species was not necessary for vaccine efficacy. CONCLUSIONS: Induction of TH1 cells that coexpress IFN-γ and TNF is not a requirement for vaccine efficacy against M. tuberculosis, despite these cytokines being essential for control of M. tuberculosis in nonvaccinated animals.
BACKGROUND: Mycobacterium tuberculosis infects one third of the world's population and causes >8 million cases of tuberculosis annually. New vaccines are necessary to control the spread of tuberculosis. T cells, interferon γ (IFN-γ), and tumor necrosis factor (TNF) are necessary to control M. tuberculosis infection in both humans and unvaccinated experimental animal models. However, the immune responses necessary for vaccine efficacy against M. tuberculosis have not been defined. The multifunctional activity of T-helper type 1 (TH1) cells that simultaneously produce IFN-γ and TNF has been proposed as a candidate mechanism of vaccine efficacy. METHODS: We used a mouse model of T-cell transfer and aerosolized M. tuberculosis infection to assess the contributions of TNF, IFN-γ, and inducible nitric oxide synthase (iNOS) to vaccine efficacy. RESULTS: CD4(+) T cells were necessary and sufficient to transfer protection against aerosolized M. tuberculosis, but neither CD4(+) T cell-produced TNF nor host cell responsiveness to IFN-γ were necessary. Transfer of Tnf(-/-) CD4(+) T cells from vaccinated donors to Ifngr(-/-) recipients was also sufficient to confer protection. Activation of iNOS to produce reactive nitrogen species was not necessary for vaccine efficacy. CONCLUSIONS: Induction of TH1 cells that coexpress IFN-γ and TNF is not a requirement for vaccine efficacy against M. tuberculosis, despite these cytokines being essential for control of M. tuberculosis in nonvaccinated animals.
Authors: L Madsen; N Labrecque; J Engberg; A Dierich; A Svejgaard; C Benoist; D Mathis; L Fugger Journal: Proc Natl Acad Sci U S A Date: 1999-08-31 Impact factor: 11.205
Authors: Sylvie Bertholet; Gregory C Ireton; Diane J Ordway; Hillarie Plessner Windish; Samuel O Pine; Maria Kahn; Tony Phan; Ian M Orme; Thomas S Vedvick; Susan L Baldwin; Rhea N Coler; Steven G Reed Journal: Sci Transl Med Date: 2010-10-13 Impact factor: 17.956
Authors: J L Flynn; M M Goldstein; J Chan; K J Triebold; K Pfeffer; C J Lowenstein; R Schreiber; T W Mak; B R Bloom Journal: Immunity Date: 1995-06 Impact factor: 31.745
Authors: Thomas Lindenstrøm; Else Marie Agger; Karen S Korsholm; Patricia A Darrah; Claus Aagaard; Robert A Seder; Ida Rosenkrands; Peter Andersen Journal: J Immunol Date: 2009-06-15 Impact factor: 5.422
Authors: Mark T Orr; Christopher B Fox; Susan L Baldwin; Sandra J Sivananthan; Elyse Lucas; Susan Lin; Tony Phan; James J Moon; Thomas S Vedvick; Steven G Reed; Rhea N Coler Journal: J Control Release Date: 2013-08-09 Impact factor: 9.776
Authors: P Ye; F H Rodriguez; S Kanaly; K L Stocking; J Schurr; P Schwarzenberger; P Oliver; W Huang; P Zhang; J Zhang; J E Shellito; G J Bagby; S Nelson; K Charrier; J J Peschon; J K Kolls Journal: J Exp Med Date: 2001-08-20 Impact factor: 14.307
Authors: Rhea N Coler; Malcolm S Duthie; Kimberly A Hofmeyer; Jeffery Guderian; Lakshmi Jayashankar; Julie Vergara; Tom Rolf; Ayesha Misquith; John D Laurance; Vanitha S Raman; H Remy Bailor; Natasha Dubois Cauwelaert; Steven J Reed; Aarthy Vallur; Michelle Favila; Mark T Orr; Jill Ashman; Prakash Ghosh; Dinesh Mondal; Steven G Reed Journal: Clin Transl Immunology Date: 2015-04-10
Authors: Susan L Baldwin; Valerie A Reese; Po-Wei D Huang; Elyse A Beebe; Brendan K Podell; Steven G Reed; Rhea N Coler Journal: Clin Vaccine Immunol Date: 2015-12-09
Authors: Mark T Orr; Elyse A Beebe; Thomas E Hudson; David Argilla; Po-Wei D Huang; Valerie A Reese; Christopher B Fox; Steven G Reed; Rhea N Coler Journal: Vaccine Date: 2015-11-03 Impact factor: 3.641
Authors: Shunsuke Sakai; Keith D Kauffman; Michelle A Sallin; Arlene H Sharpe; Howard A Young; Vitaly V Ganusov; Daniel L Barber Journal: PLoS Pathog Date: 2016-05-31 Impact factor: 6.823
Authors: K D Kauffman; M A Sallin; S Sakai; O Kamenyeva; J Kabat; D Weiner; M Sutphin; D Schimel; L Via; C E Barry; T Wilder-Kofie; I Moore; R Moore; D L Barber Journal: Mucosal Immunol Date: 2017-07-26 Impact factor: 7.313
Authors: Rolf Billeskov; Esterlina V Tan; Marjorie Cang; Rodolfo M Abalos; Jasmin Burgos; Bo Vestergaard Pedersen; Dennis Christensen; Else Marie Agger; Peter Andersen Journal: PLoS One Date: 2016-08-15 Impact factor: 3.240
Authors: Rolf Billeskov; Thomas Lindenstrøm; Joshua Woodworth; Cristina Vilaplana; Pere-Joan Cardona; Joseph P Cassidy; Rasmus Mortensen; Else Marie Agger; Peter Andersen Journal: Front Immunol Date: 2018-01-15 Impact factor: 7.561