Increased (6 exon) interleukin-7 production after M. tuberculosis infection and soluble interleukin-7 receptor expression in lung tissue

• Published in: Genes and immunity Vol. 12; no. 7; pp. 513 - 522
• Main Authors: Rane, L, Rahman, S, Magalhaes, I, Ahmed, R, Spångberg, M, Kondova, I, Verreck, F, Andersson, J, Brighenti, S, Maeurer, M J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2011; Nature Publishing Group
• Subjects: 631/250/127/1213; 631/337/1645/1946; 692/699/255/1856; Alternative Splicing; Animal models; Animals; BCG; BCG Vaccine - immunology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cytokines; Exons; Female; gamma -Interferon; Gene Expression; Gene Expression Regulation; Genes; Genetic aspects; Haplotypes; Human Genetics; Immune system; Immunology; Infection; Infections; Infectious diseases; Interleukin 17; Interleukin 7; Interleukin-7 - biosynthesis; Interleukin-7 - genetics; Isoforms; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Lung; Lung - immunology; Lungs; Lymph nodes; Lymphatic system; Lymphocyte Activation - immunology; Macaca mulatta; Medicin och hälsovetenskap; Monkeys & apes; Multiple sclerosis; Mycobacterium tuberculosis; original-article; Peripheral blood mononuclear cells; Physiological aspects; Primates; Receptors, Interleukin-7 - genetics; Spleen; Survival; T-Lymphocytes - immunology; Transforming growth factor- beta; Transforming growth factor-b; Transforming growth factors; Tuberculosis; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - pathology; Vaccination; Virulence; γ-Interferon; Netherlands; Sweden; non-human primate; differential splicing; T cells; interleukin-7; IL-7 receptor
• ISSN: 1466-4879; 1476-5470; 1476-5470
• DOI: 10.1038/gene.2011.29

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.