Mycobacterium tuberculosis infection induces il12rb1 splicing to generate a novel IL-12Rβ1 isoform that enhances DC migration

Richard T. Robinson, Shabaana A. Khader, Cynthia A. Martino, Jeffrey J. Fountain, Maria Teixeira-Coelho, John E. Pearl, Stephen T. Smiley, Gary M. Winslow, David L. Woodland, Michael J. Walter, Jose R. Conejo-Garcia, Ueli Gubler, Andrea M. Cooper

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

RNA splicing is an increasingly recognized regulator of immunity. Here, we demonstrate that after Mycobacterium tuberculosis infection (mRNA) il12rb1 is spliced by dendritic cells (DCs) to form an alternative (mRNA) il12rb1Δtm that encodes the protein IL-12Rβ1ΔTM. Compared with IL-12Rβ1, IL-12Rβ1ΔTM contains an altered C-terminal sequence and lacks a transmembrane domain. Expression of IL-12Rβ1ΔTM occurs in CD11c + cells in the lungs during M. tuberculosis infection. Selective reconstitution of il12rb1-/- DCs with (mRNA) il12rb1 and/or (mRNA) il12rb1Δtm demonstrates that IL-12Rβ1Δaugments IL-12Rβ1-dependent DC migration and activation of M. tuberculosis-specific T cells. It cannot mediate these activities independently of IL12Rβ1. We hypothesize that M. tuberculosis-exposed DCs express IL-12Rβ1ΔTM to enhance IL-12Rβ1-dependent migration and promote M. tuberculosis-specific T cell activation. IL-12Rβ1ΔTM thus represents a novel positive-regulator of IL12Rβ1-dependent DC function and of the immune response to M. tuberculosis.

Original languageEnglish
Pages (from-to)591-605
Number of pages15
JournalJournal of Experimental Medicine
Volume207
Issue number3
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

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    Robinson, R. T., Khader, S. A., Martino, C. A., Fountain, J. J., Teixeira-Coelho, M., Pearl, J. E., Smiley, S. T., Winslow, G. M., Woodland, D. L., Walter, M. J., Conejo-Garcia, J. R., Gubler, U., & Cooper, A. M. (2010). Mycobacterium tuberculosis infection induces il12rb1 splicing to generate a novel IL-12Rβ1 isoform that enhances DC migration. Journal of Experimental Medicine, 207(3), 591-605. https://doi.org/10.1084/jem.20091085