| First Author | Bai X | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 16 | Pages | 5111-6 |
| PubMed ID | 25820174 | Mgi Jnum | J:220820 |
| Mgi Id | MGI:5636528 | Doi | 10.1073/pnas.1424302112 |
| Citation | Bai X, et al. (2015) Human IL-32 expression protects mice against a hypervirulent strain of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 112(16):5111-6 |
| abstractText | Silencing of interleukin-32 (IL-32) in a differentiated human promonocytic cell line impairs killing of Mycobacterium tuberculosis (MTB) but the role of IL-32 in vivo against MTB remains unknown. To study the effects of IL-32 in vivo, a transgenic mouse was generated in which the human IL-32gamma gene is expressed using the surfactant protein C promoter (SPC-IL-32gammaTg). Wild-type and SPC-IL-32gammaTg mice were infected with a low-dose aerosol of a hypervirulent strain of MTB (W-Beijing HN878). At 30 and 60 d after infection, the transgenic mice had 66% and 85% fewer MTB in the lungs and 49% and 68% fewer MTB in the spleens, respectively; the transgenic mice also exhibited greater survival. Increased numbers of host-protective innate and adaptive immune cells were present in SPC-IL-32gammaTg mice, including tumor necrosis factor-alpha (TNFalpha) positive lung macrophages and dendritic cells, and IFN-gamma (IFNgamma) and TNFalpha positive CD4(+) and CD8(+) T cells in the lungs and mediastinal lymph nodes. Alveolar macrophages from transgenic mice infected with MTB ex vivo had reduced bacterial burden and increased colocalization of green fluorescent protein-labeled MTB with lysosomes. Furthermore, mouse macrophages made to express IL-32gamma but not the splice variant IL-32beta were better able to limit MTB growth than macrophages capable of producing both. The lungs of patients with tuberculosis showed increased IL-32 expression, particularly in macrophages of granulomas and airway epithelial cells but also B cells and T cells. We conclude that IL-32gamma enhances host immunity to MTB. |
