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CD30 is required for activation of a unique subset of interleukin-17A-producing ?? T cells in innate immunity against Mycobacterium bovis Bacillus Calmette-Guerin infection.

ABSTRACT: Interleukin-17A (IL-17A)-producing ?? T cells are known to be activated following Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. Here, we show that CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is important for activation of IL-17A-producing ?? T cells after BCG infection. V?1(-) V?4(-) ?? T cells preferentially expressing V?6/V?1 genes were identified as the major source of IL-17A in the peritoneal cavity during the early stage of BCG infection. The number of IL-17A-producing V?1(-) V?4(-) ?? T cells bearing V?6 increased in peritoneal exudate cells (PEC) of wild-type (WT) mice but not in those of CD30 knockout (KO) mice in response to BCG infection. Consistently, CD30 ligand (CD30L) or CD30 expression, predominantly by V?1(-) V?4(-) ?? T cells, was rapidly upregulated after BCG infection. Inhibition of CD30L/CD30 signaling by in vivo administration of a soluble CD30 and immunoglobulin fusion protein (CD30-Ig) severely impaired activation of IL-17A-producing V?1(-) V?4(-) ?? T cells in WT mice, while stimulating CD30L/CD30 signaling by in vivo administration of agonistic anti-CD30 monoclonal antibody (MAb) restored IL-17A production by V?1(-) V?4(-) ?? T cells in CD30L KO mice after BCG infection. These results suggest that CD30 signaling plays an important role in the activation of IL-17A-producing V?1(-) V?4(-) ?? T cells bearing V?6 at an early stage of BCG infection.

SUBMITTER: Guo Y

PROVIDER: S-EPMC3811784 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

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CD30 is required for activation of a unique subset of interleukin-17A-producing γδ T cells in innate immunity against Mycobacterium bovis Bacillus Calmette-Guerin infection.

Guo Ying Y Sun Xun X Shibata Kensuke K Yamada Hisakata H Muta Hiromi H Podack Eckhard R ER Yoshikai Yasunobu Y

Infection and immunity 20130805 10

Interleukin-17A (IL-17A)-producing γδ T cells are known to be activated following Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. Here, we show that CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is important for activation of IL-17A-producing γδ T cells after BCG infection. Vγ1(-) Vγ4(-) γδ T cells preferentially expressing Vγ6/Vδ1 genes were identified as the major source of IL-17A in the peritoneal cavity during the early stage of BCG infection. The numb ...[more]

PMID: 23918785

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Project description:Mycobacterium tuberculosis and Mycobacterium bovis bacille Calmette-Guérin (BCG) alter the maturation of their phagosomes and reside within a compartment that resists acidification and fusion with lysosomes. To define the molecular composition of this compartment, we developed a novel method for obtaining highly purified phagosomes from BCG-infected human macrophages and analyzed the phagosomes by Western immunoblotting and mass spectrometry-based proteomics. Our purification procedure revealed that BCG grown on artificial medium becomes less dense after growth in macrophages. By Western immunoblotting, LAMP-2, Niemann-Pick protein C1, and syntaxin 3 were readily detectable on the BCG phagosome but at levels that were lower than on the latex bead phagosome; flotillin-1 and the vacuolar ATPase were barely detectable on the BCG phagosome but highly enriched on the latex bead phagosome. Immunofluorescence studies confirmed the scarcity of flotillin on BCG phagosomes and demonstrated an inverse correlation between bacterial metabolic activity and flotillin on M. tuberculosis phagosomes. By mass spectrometry, 447 human host proteins were identified on BCG phagosomes, and a partially overlapping set of 289 human proteins on latex bead phagosomes was identified. Interestingly, the majority of the proteins identified consistently on BCG phagosome preparations were also identified on latex bead phagosomes, indicating a high degree of overlap in protein composition of these two compartments. It is likely that many differences in protein composition are quantitative rather than qualitative in nature. Despite the remarkable overlap in protein composition, we consistently identified a number of proteins on the BCG phagosomes that were not identified in any of our latex bead phagosome preparations, including proteins involved in membrane trafficking and signal transduction, such as Ras GTPase-activating-like protein IQGAP1, and proteins of unknown function, such as FAM3C. Our phagosome purification procedure and initial proteomics analyses set the stage for a quantitative comparative analysis of mycobacterial and latex bead phagosome proteomes.

Dataset Information

CD30 is required for activation of a unique subset of interleukin-17A-producing ?? T cells in innate immunity against Mycobacterium bovis Bacillus Calmette-Guerin infection.

Publications

CD30 is required for activation of a unique subset of interleukin-17A-producing γδ T cells in innate immunity against Mycobacterium bovis Bacillus Calmette-Guerin infection.

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