title: Increased (6 exon) interleukin-7 production after M. tuberculosis infection and soluble interleukin-7 receptor expression in lung tissue.
abstract: Interleukin-7 (IL-7) and the IL-7 receptor (IL-7R) have been shown to be alternatively spliced in infectious diseases. We tested IL-7 and IL-7R splicing in a tuberculosis (TB)-vaccine/Mycobacterium tuberculosis (Mtb)-challenge model in non-human primates (NHPs). Differential IL-7 splicing was detected in peripheral blood mononuclear cells (PBMCs) from 15/15 NHPs showing 6 different IL-7 spliced isoforms. This pattern did not change after infection with virulent Mtb. We demonstrated increased IL-7 (6 exon) and IL-17 protein production in lung tissue along with concomitant decreased transforming growth factor-β (TGF-β) from NHPs (vaccinated with a recombinant BCG (rBCG)) who showed increased survival after Mtb challenge. IL-7 increased IL-17 and interferon-γ (IFN-γ) gene and protein expression in PBMCs. Mtb-infected NHPs showed differential IL-7R splicing associated with the anatomical location and tissue origin, that is, in lung tissue, hilus, axillary lymph nodes (LNs) and spleen. Differential splicing of the IL-7R was typical for healthy (non-Mtb infected) and for Mtb-infected lung tissue with a dominant expression of soluble IL-7R (sIL-7R) receptor lacking exon 6 (9:1 ratio of sIL-7R/cell-bound IL-7R). Differential ratios of cell-bound vs sIL-7R could be observed in hilus and axillary LNs from Mtb-infected NHPs with an inversed ratio of 1:9 (sIL-7R/cell-bound IL-7R) in spleen and PBMCs. Soluble IL-7R is exclusively present in lung tissue.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Rane
authors.forename: S
authors.initials: S
authors.lastname: Rahman
authors.forename: I
authors.initials: I
authors.lastname: Magalhaes
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
authors.forename: M
authors.initials: M
authors.lastname: Spångberg
authors.forename: I
authors.initials: I
authors.lastname: Kondova
authors.forename: F
authors.initials: F
authors.lastname: Verreck
authors.forename: J
authors.initials: J
authors.lastname: Andersson
authors.forename: S
authors.initials: S
authors.lastname: Brighenti
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D009169:Mycobacterium tuberculosis; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D001500:BCG Vaccine; D015851:Interleukin-7; D020395:Receptors, Interleukin-7