| First Author | Ray AA | Year | 2015 |
| Journal | Infect Immun | Volume | 83 |
| Issue | 2 | Pages | 560-71 |
| PubMed ID | 25404030 | Mgi Jnum | J:316896 |
| Mgi Id | MGI:6837494 | Doi | 10.1128/IAI.01230-13 |
| Citation | Ray AA, et al. (2015) IL12Rbeta1DeltaTM is a secreted product of il12rb1 that promotes control of extrapulmonary tuberculosis. Infect Immun 83(2):560-71 |
| abstractText | IL12RB1 is a human gene that is important for resistance to Mycobacterium tuberculosis infection. IL12RB1 is expressed by multiple leukocyte lineages, and encodes a type I transmembrane protein (IL12Rbeta1) that associates with IL12p40 and promotes the development of host-protective T(H)1 cells. Recently, we observed that il12rb1-the mouse homolog of IL12RB1-is alternatively spliced by leukocytes to produce a second isoform (IL12Rbeta1DeltaTM) that has biological properties distinct from IL12Rbeta1. Although the expression of IL12Rbeta1DeltaTM is elicited by M. tuberculosis in vivo, and its overexpression enhances IL12p40 responsiveness in vitro, the contribution of IL12Rbeta1DeltaTM to controlling M. tuberculosis infection has not been tested. Here, we demonstrate that IL12Rbeta1DeltaTM represents a secreted product of il12rb1 that, when absent from mice, compromises their ability to control M. tuberculosis infection in extrapulmonary organs. Furthermore, elevated M. tuberculosis burdens in IL12Rbeta1DeltaTM-deficient animals are associated with decreased lymph node cellularity and a decline in TH1 development. Collectively, these data support a model wherein IL12Rbeta1DeltaTM is a secreted product of il12rb1 that promotes resistance to M. tuberculosis infection by potentiating T(H) cells response to IL-12. |
