title: IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response toMycobacterium tuberculosis.
abstract: The programed death-1 (PD-1)-programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies ofMycobacterium tuberculosis. Specifically,M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response toM. tuberculosishas not been investigated. In the present report, we demonstrate thatM. tuberculosisandM. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4+T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response toM. tuberculosis. Together, our results indicate that IL-1β, but not members of the programed death pathway, is critical for human Th17 response toM. tuberculosis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; UMR S 1138, Sorbonne Universités, UPMC Univ Paris, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stephen-Victor
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France.
authors.forename: Varun Kumar
authors.initials: VK
authors.lastname: Sharma
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; UMR S 1138, Sorbonne Universités, UPMC Univ Paris, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France.
authors.forename: Mrinmoy
authors.initials: M
authors.lastname: Das
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; UMR S 1138, Sorbonne Universités, UPMC Univ Paris, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France.
authors.forename: Anupama
authors.initials: A
authors.lastname: Karnam
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France.
authors.forename: Chaitrali
authors.initials: C
authors.lastname: Saha
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; UMR S 1138, Sorbonne Universités, UPMC Univ Paris, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France; UMR S 1138, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lecerf
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; UMR S 1138, Sorbonne Universités, UPMC Univ Paris, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Galeotti
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; UMR S 1138, Sorbonne Universités, UPMC Univ Paris, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France; UMR S 1138, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, France; UMR S 1138, Sorbonne Universités, UPMC Univ Paris, Paris, France; Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France; UMR S 1138, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
keywords: IL-1β; IL-23; Mycobacterium tuberculosis; PD-1; PD-L1; Th17; dendritic cells; monocytes