Journal
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
Volume 205, Issue 3, Pages 219-229Publisher
SPRINGER
DOI: 10.1007/s00430-015-0442-x
Keywords
Granulysin; Tuberculosis; Hypoxia; Human; Infectious immunity
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Funding
- Institute for Transfusion Medicine, University Hospital Ulm
- European Union [TBVAC2020]
- Land-Baden-Wurttemberg (Kooperative Promotionskolleg Phamazeutische Biotechnologie der Hochschule Biberach und der Universitat Ulm)
- International Graduate School in Molecular Medicine Ulm
- graduate school Experimentelle Medizin der Universitat Ulm
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Oxygen tension affects local immune responses in inflammation and infection. In tuberculosis mycobacteria avoid hypoxic areas and preferentially persist and reactivate in the oxygen-rich apex of the lung. Oxygen restriction activates antimicrobial effector mechanisms in macrophages and restricts growth of intracellular Mycobacterium tuberculosis (M.Tb). The effect of oxygen restriction on T cell-mediated antimicrobial effector mechanisms is unknown. Therefore we determined the influence of hypoxia on the expression of granulysin, an antimicrobial peptide of lymphocytes. Hypoxia increased the antigen-specific up-regulation of granulysin mRNA and protein in human CD4(+) and CD8(+) T lymphocytes. This observation was functionally relevant, because oxygen restriction supported the growth-limiting effect of antigen-specific T cells against virulent M.Tb residing in primary human macrophages. Our results provide evidence that oxygen restriction promotes the expression of granulysin and suggest that this effect-in conjunction with additional T cell-mediated immune responses-supports protection against mycobacteria. The therapeutic modulation of oxygen availability may offer a new strategy for the host-directed therapy of infectious diseases with intracellular pathogens.
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