Th17 cytokines in recall responses against Francisella tularensis in humans.

To determine whether cytokines and T-cell subsets other than Th1 cells contribute to secondary immune responses against Francisella species, we investigated production of Th17-associated cytokines IL-17 and IL-22 in a recall response to Francisella tularensis. Peripheral blood mononuclear cells (PBMCs) from volunteers previously immunized with the F. tularensis live vaccine strain (LVS) were stimulated in vitro with bacterial lysates of LVS or a nonpathogenic type A B38 strain. Gene expression analysis by real-time PCR showed that IL-17 and IL-22 transcripts were induced in immune PBMCs at a significantly higher level than in cells from nonvaccinated volunteers stimulated with LVS or B38 antigens at 24 h. In addition, we detected both cell-associated and secreted IL-22 at 24 h after stimulation and IL-17 at 72 h post-stimulation. Intracellular IL-22 and IL-17 were observed in memory CD4+ cells and less in memory CD8+ cells. These findings suggest that Th17 responses in addition to the Th1 response may play an important role in adaptive immunity against Francisella.

[1]  S. Way,et al.  Interleukin‐17 in host defence against bacterial, mycobacterial and fungal pathogens , 2009, Immunology.

[2]  D. Metzger,et al.  Humoral and cell‐mediated immunity to the intracellular pathogen Francisella tularensis , 2008, Immunological reviews.

[3]  R. Wilkinson,et al.  Distinct, Specific IL-17- and IL-22-Producing CD4+ T Cell Subsets Contribute to the Human Anti-Mycobacterial Immune Response1 , 2008, The Journal of Immunology.

[4]  S. Galli,et al.  Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL‐17 , 2007, Journal of leukocyte biology.

[5]  R. Locksley,et al.  IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge , 2007, Nature Immunology.

[6]  K. Mills,et al.  TLR4 Mediates Vaccine-Induced Protective Cellular Immunity to Bordetella pertussis: Role of IL-17-Producing T Cells1 , 2006, The Journal of Immunology.

[7]  L. Fouser,et al.  Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides , 2006, The Journal of experimental medicine.

[8]  L. Harrington,et al.  Expanding the effector CD4 T-cell repertoire: the Th17 lineage. , 2006, Current opinion in immunology.

[9]  R. D. Hatton,et al.  Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages , 2005, Nature Immunology.

[10]  Ying Wang,et al.  A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 , 2005, Nature Immunology.

[11]  K. Hiromura,et al.  Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. , 2005, Arthritis and rheumatism.

[12]  A. Lindén,et al.  Interleukin-17 family members and inflammation. , 2004, Immunity.

[13]  P. Iribarren,et al.  Chemokines and chemokine receptors: their manifold roles in homeostasis and disease. , 2004, Cellular & molecular immunology.

[14]  S. Ferretti,et al.  IL-17, Produced by Lymphocytes and Neutrophils, Is Necessary for Lipopolysaccharide-Induced Airway Neutrophilia: IL-15 as a Possible Trigger , 2003, The Journal of Immunology.

[15]  Philip K. Russell,et al.  Tularemia as a biological weapon: medical and public health management. , 2001, JAMA.

[16]  W. Maśliński,et al.  High Levels of IL-17 in Rheumatoid Arthritis Patients: IL-15 Triggers In Vitro IL-17 Production Via Cyclosporin A-Sensitive Mechanism1 , 2000, The Journal of Immunology.

[17]  H. Surcel,et al.  Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings , 1991, Journal of clinical microbiology.

[18]  A. Tärnvik,et al.  Several membrane polypeptides of the live vaccine strain Francisella tularensis LVS stimulate T cells from naturally infected individuals , 1990, Journal of clinical microbiology.

[19]  A. Tärnvik.  Nature of protective immunity to Francisella tularensis. , 1989, Reviews of infectious diseases.

[20]  C. Fathman,et al.  Modulation of CD4 by antigenic activation. , 1987, Journal of immunology.

[21]  H. T. Eigelsbach,et al.  Prophylactic effectiveness of live and killed tularemia vaccines. I. Production of vaccine and evaluation in the white mouse and guinea pig. , 1961, Journal of immunology.

[22]  H. Wilson,et al.  Tularemia vaccine study. I. Intracutaneous challenge. , 1961, Archives of internal medicine.

[23]  H. Wilson,et al.  Tularemia vaccine study. II. Respiratory challenge. , 1961, Archives of internal medicine.

[24]  A. Tärnvik,et al.  Long-lasting recall response of CD4+ and CD8+ αβ T cells, but not γδ T cells, to heat shock proteins of Francisella tularensis. , 2001 .

[25]  D. Burke.  Immunization against tularemia: analysis of the effectiveness of live Francisella tularensis vaccine in prevention of laboratory-acquired tularemia. , 1977, The Journal of infectious diseases.