IL-10 Blocks Phagosome Maturation in Mycobacterium tuberculosis-infected Human Macrophages.

O'Leary, S., O'Sullivan, M.P., Keane, J.
Journal   Am J Respir Cell Mol Biol.
Species  
Analytes Measured   IL-10
Matrix Tested   Cell culture supernatants
Year   2011
Volume  
Page Numbers  
Application   Cytokines and Chemokines
Abstract
Successful phagolysosomal maturation is an important innate immune response to intracellular infection. However, Mycobacterium tuberculosis (Mtb) can manipulate and inhibit this host response to ensure survival within its niche cell. We investigate the role of the anti-inflammatory cytokine IL-10 on Mtb-phagosome maturation. Blocking IL-10, which was secreted from Mtb-infected macrophages, allowed phagosome maturation to proceed. Macrophage cytokine gene expression profiles were not significantly altered by blocking IL-10 3 hours after infection with Mtb. We demonstrate that IL-10 can regulate this protective phenotype in phorbol myristate acetate (PMA)-treated THP-1 cells, monocyte-derived macrophages (MDMs), and human alveolar macrophages (AMs) infected with Mtb. The regulatory effect of endogenous IL-10 was evident in macrophages infected with virulent Mtb H37Rv, as well as in attenuated strains of mycobacteria. Unlike live Mtb, dead bacilli occupy a mature, acidic phagosome. However, the addition of IL-10 to cells infected with killed Mtb successfully inhibited the maturation of this compartment. Importantly, we demonstrate that the addition of IL-10 to MDMs results in enhanced mycobacterial survival and growth. Our results suggest that IL-10 exerts its effects on this early macrophage response in a partly signal transducer and activator of transcription 3 (STAT3)-dependent manner, and independent of mitogen activated protein kinase p38 (MAPKp38) and extracellular regulated kinase 1/2 (ERK1/2) activity. IL-10 is a feature of human tuberculous granuloma, and these new findings support the hypothesis that this cytokine can promote pathogen persistence by contributing to Mtb-phagosome maturation arrest in human macrophages.

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V-PLEX Human Cytokine 29-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-10 Kit
IL-10 | Human
Singleplex
V-PLEX Mouse IL-10 Kit
IL-10 | Mouse
Singleplex
V-PLEX Plus Human Cytokine 29-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Plus Human IL-10 Kit
IL-10 | Human
Singleplex
V-PLEX Plus Mouse IL-10 Kit
IL-10 | Mouse
Singleplex
V-PLEX Plus Proinflammatory Panel 1 Mouse Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Multiplex
V-PLEX Plus Rat IL-10 Kit
IL-10 | Rat
Singleplex
V-PLEX Plus Proinflammatory Panel 1 Human Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
V-PLEX Proinflammatory Panel 1 Human Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
V-PLEX Proinflammatory Panel 1 Mouse Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Multiplex
V-PLEX Rat IL-10 Kit
IL-10 | Rat
Singleplex
Proinflammatory Panel 1 Human Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Proinflammatory Panel 1 Mouse Control Pack
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, KC/GRO, TNF-α | Mouse
Proinflammatory Panel 1 Rat Control Pack
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
V-PLEX Custom Mouse Biomarkers
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, TNF-α | Mouse
Multiplex
V-PLEX Custom Rat Biomarkers
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Multiplex
Canine IL-10 Ultra-Sensitive Kit
IL-10 | Canine
Singleplex
Human IL-10 Antibody
IL-10
Rat IL-10 Antibody
IL-10
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