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

Genes & Immunity volume 12, pages 513–522 (2011)Cite this article

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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.

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Acknowledgements

The study has been supported by VR, Vinnova, HLF, Sweden and the Aeras foundation, USA to MM, Lalit Rane received a KID grant from KI, Sweden.

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  1. L Rane and S Rahman: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden

    L Rane, I Magalhaes & M J Maeurer

  2. Department of Medicine, Center for Infectious Medicine (CIM), Karolinska University Hospital, Stockholm, Sweden

    S Rahman, J Andersson & S Brighenti

  3. CAST, Karolinska Hospital, Stockholm, Sweden

    I Magalhaes & M J Maeurer

  4. Smittskyddsinstitutet, Stockholm, Sweden

    R Ahmed & M Spångberg

  5. BPRC, Rijswijk, The Netherlands

    I Kondova & F Verreck

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Correspondence to M J Maeurer.

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Rane, L., Rahman, S., Magalhaes, I. et al. Increased (6 exon) interleukin-7 production after M. tuberculosis infection and soluble interleukin-7 receptor expression in lung tissue. Genes Immun 12, 513–522 (2011). https://doi.org/10.1038/gene.2011.29

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