Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10.
BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3338562?pdf=render |
| _version_ | 1818542515372949504 |
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| author | Carmen A Ambarus Kim C M Santegoets Lenny van Bon Mark H Wenink Paul P Tak Timothy R D J Radstake Dominique L P Baeten |
| author_facet | Carmen A Ambarus Kim C M Santegoets Lenny van Bon Mark H Wenink Paul P Tak Timothy R D J Radstake Dominique L P Baeten |
| author_sort | Carmen A Ambarus |
| collection | DOAJ |
| description | BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-γ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs). Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MΦ(IL-4). In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2). The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10. |
| first_indexed | 2024-12-11T22:23:06Z |
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| id | doaj.art-24a7f0c60f974a33a5cd31f5e96d39f4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:23:06Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-24a7f0c60f974a33a5cd31f5e96d39f42022-12-22T00:48:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3599410.1371/journal.pone.0035994Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10.Carmen A AmbarusKim C M SantegoetsLenny van BonMark H WeninkPaul P TakTimothy R D J RadstakeDominique L P BaetenBACKGROUND: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-γ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs). Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MΦ(IL-4). In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2). The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10.http://europepmc.org/articles/PMC3338562?pdf=render |
| spellingShingle | Carmen A Ambarus Kim C M Santegoets Lenny van Bon Mark H Wenink Paul P Tak Timothy R D J Radstake Dominique L P Baeten Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10. PLoS ONE |
| title | Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10. |
| title_full | Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10. |
| title_fullStr | Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10. |
| title_full_unstemmed | Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10. |
| title_short | Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10. |
| title_sort | soluble immune complexes shift the tlr induced cytokine production of distinct polarized human macrophage subsets towards il 10 |
| url | http://europepmc.org/articles/PMC3338562?pdf=render |
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