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

2010 ◽  
Vol 207 (3) ◽  
pp. 591-605 ◽  
Author(s):  
Richard T. Robinson ◽  
Shabaana A. Khader ◽  
Cynthia A. Martino ◽  
Jeffrey J. Fountain ◽  
Maria Teixeira-Coelho ◽  
...  

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-12Rβ1ΔTM augments 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.

1997 ◽  
Vol 186 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Andrea M. Cooper ◽  
Jeanne Magram ◽  
Jessica Ferrante ◽  
Ian M. Orme

Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation. The cytokine-mediating macrophage activation is interferon-γ (IFN-γ), which is largely dependent on interleukin-12 (IL-12) for its induction. To address the role of IL-12 in immunity to tuberculosis, IL-12 p40−/− mice were infected with M. tuberculosis and their capacity to control bacterial growth and other characteristics of their immune response were determined. The IL-12 p40−/− mice were unable to control bacterial growth and this appeared to be linked to the absence of both innate and acquired sources of IFN-γ. T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40−/− mice. Therefore, IL-12 is essential to the generation of a protective immune response to M. tuberculosis, with its main functions being the induction of the expression of IFN-γ and the activation of antigen-specific lymphocytes capable of creating a protective granuloma.


Virulence ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1227-1238
Author(s):  
Nathan Scott Kieswetter ◽  
Mumin Ozturk ◽  
Shelby-Sara Jones ◽  
Sibusiso Senzani ◽  
Melissa Dalcina Chengalroyen ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e22637 ◽  
Author(s):  
Gaetano Caramori ◽  
Lisa Lasagna ◽  
Angelo G. Casalini ◽  
Ian M. Adcock ◽  
Paolo Casolari ◽  
...  

2007 ◽  
Vol 77 (4) ◽  
pp. 691-698 ◽  
Author(s):  
Fabiani Gai Frantz ◽  
Walter Miguel Turato ◽  
Rogério Silva Rosada ◽  
Célio Lopes Silva ◽  
Lúcia Helena Faccioli ◽  
...  

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