• Proc. Natl. Acad. Sci. U.S.A. · Apr 2015

    Human IL-32 expression protects mice against a hypervirulent strain of Mycobacterium tuberculosis.

    • Xiyuan Bai, Shaobin Shang, Marcela Henao-Tamayo, Randall J Basaraba, Alida R Ovrutsky, Jennifer L Matsuda, Katsuyuki Takeda, Mallory M Chan, Azzeddine Dakhama, William H Kinney, Jessica Trostel, An Bai, Jennifer R Honda, Rosane Achcar, John Hartney, Leo A B Joosten, Soo-Hyun Kim, Ian Orme, Charles A Dinarello, Diane J Ordway, and Edward D Chan.
    • Denver Veterans Affairs Medical Center, Denver, CO 80206; Departments of Medicine and Academic Affairs, Divisions of Pulmonary Sciences and Critical Care Medicine and cdinare333@aol.com BaiX@NJHealth.org ChanE@NJHealth.org.
    • Proc. Natl. Acad. Sci. U.S.A. 2015 Apr 21; 112 (16): 5111-6.

    AbstractSilencing 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-32γ gene is expressed using the surfactant protein C promoter (SPC-IL-32γTg). Wild-type and SPC-IL-32γTg 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-32γTg mice, including tumor necrosis factor-alpha (TNFα) positive lung macrophages and dendritic cells, and IFN-gamma (IFNγ) and TNFα 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-32γ but not the splice variant IL-32β 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-32γ enhances host immunity to MTB.

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