Interleukin‐15 in Mycobacterial Infection of Antigen‐Presenting Cells

Abstract

Interleukin-15 (IL-15) shares many biological functions with IL-2 but also exhibits unique effects. Some of these represent the potent chemoattractant activity and expansion of distinct T-cell subsets, particularly memory T cells. IL-15 may therefore modulate the quality and quantity of cellular immune responses directed against intracellular pathogens. Immunohistochemical examination of skin lesions obtained from patients with the lepromatous or the tuberculoid form of Hansen's disease revealed intralesional IL-15 protein in both forms of the disease. In addition to Mycobacterium leprae, a number of different mycobacterial species are capable of effectively inducing IL-15 secretion in infected macrophages. In this work, increased IL-15 secretion was observed in IL-4/granulocyte-macrophage colony-stimulating factor (GM-CSF)-activated antigen-presenting cells (APC) compared with unstimulated macrophages. Immunocytological detection of intracellular IL-15 revealed that infection with different mycobacterial species resulted in different staining patterns of anti-IL-15 immunoreactive material in APC. In contrast to IL-2 or IL-7, IL-15 enhanced the cytolytic potential of immune effector cells in vitro and favoured the expansion of CD1b-restricted immune cells recognizing mycobacterial-associated antigens presented by autologous APC. IL-15 produced by infected cells in situ may represent one of the key cytokines involved in granuloma formation and may aid the augmentation of cellular immune responses directed against mycobacterial-infected cells.

Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis

“…The finding of increased IL-15 gene expression in the lungs of our patients with sarcoidosis is consistent with those of Muro and colleagues (26) and with experimental evidence linking IL-15 to macrophage-T-cell interactions in patients with active sarcoidosis (27). IL-15 expression in macrophages is regulated by IL-4 and GM-CSF, a mechanism favoring granuloma formation in the context of infections (28). IL-15 is highly expressed in alveolar macrophages derived from patients with sarcoidosis and is shown to induce the release of IFN-g from T cells (27).…”

Effect of Apoptotic Cell Recognition on Macrophage Polarization and Mycobacterial Persistence

“…IL-15 may represent a key cytokine involved in granuloma formation and may enhance cellular immune responses to mycobacterial antigens (15,50). Our data showed that macrophage differentiation in vitro with GM-CSF induced increased levels of IL-15, reinforcing our hypothesis that these cells exhibit the phenotype of macrophages found in paucibacillary patients.…”

Molecular and Functional Characterization of IL-15 in Rainbow TroutOncorhynchus mykiss:A Potent Inducer of IFN-γ Expression in Spleen Leukocytes

“…Although IL-15 is constitutively expressed in cells of the monocyte/macrophage lineage, the expression of IL-15 mRNA has been shown to be up-regulated by LPS, poly I:C, as well as bacterial (12,81,82) and viral (83) infection. The present results show clearly that IFN-␥ is an important immune regulator of IL-15 in fish.…”

“…The production of bioactive membrane bound or secreted IL-15 in mammals appears to be tightly controlled (81,84). Enhanced IL-15 protein production results from either increased transcription and/or stability of IL-15 mRNA, posttranslational modification, or altered cellular trafficking, and enhanced release of already preformed intracellular IL-15 protein.…”