title: An anti-inflammatory role for V alpha 14 NK T cells in Mycobacterium bovis bacillus Calmette-Guérin-infected mice.
abstract: The possible contribution of NKT cells to resistance to Mycobacterium tuberculosis infection remains unclear. In this paper we characterized the Valpha14 NKT cell population following infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). BCG infection determined an early expansion of Valpha14 NKT cells in liver, lungs, and spleen, which peaked on day 8 and was sustained until day 30. However, an NK1.1(+) Valpha14 NKT population preferentially producing IFN-gamma predominated at an early stage (day 8), which was substituted by an NK1.1(-) population preferentially producing IL-4 at later stages (day 30). Despite the fact that Valpha14 NKT cell-deficient mice eliminated BCG as did control mice, they had significantly higher numbers of granulomas in liver and lungs. Additionally, while control mice developed organized small granulomas, those in Valpha14 NKT-deficient mice had signs of caseation, large cellular infiltrates, and some multinucleated macrophages, suggesting that Valpha14 NKT cells may actually work as anti-inflammatory cells by limiting excessive lymphocyte influx and tissue pathology. In agreement, we found an increased spontaneous production and mRNA expression of TNF-alpha in liver and lungs of Valpha14 NKT-deficient mice, whose neutralization in vivo by anti-TNF-alpha mAbs consistently reduced the number of granulomas in liver and lungs. Together, our results support a regulatory role for Valpha14 NKT cells in the course of BCG infection through their ability to limit the extent of inflammatory response and point to an important role for this cell subset as a regulator of the balance between protective responses and immunopathology.
authors.affiliation: Department of Biopathology, University of Palermo, Palermo, Italy. dieli@unipa.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Stephane
authors.initials: S
authors.lastname: Sidobre
authors.forename: Juraj
authors.initials: J
authors.lastname: Ivanyi
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Fattorini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iona
authors.forename: Graziella
authors.initials: G
authors.lastname: Orefici
authors.forename: Giacomo
authors.initials: G
authors.lastname: De Leo
authors.forename: Domenica
authors.initials: D
authors.lastname: Russo
authors.forename: Nadia
authors.initials: N
authors.lastname: Caccamo
authors.forename: Guido
authors.initials: G
authors.lastname: Sireci
authors.forename: Caterina
authors.initials: C
authors.lastname: Di Sano
authors.forename: Alfredo
authors.initials: A
authors.lastname: Salerno
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D006099:Granuloma / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma