PMID- 16330536 OWN - NLM STAT- MEDLINE DCOM- 20060511 LR - 20220409 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 79 IP - 2 DP - 2006 Feb TI - Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation. PG - 285-93 AB - Macrophages (Mphi) comprise a heterogeneous population of cells with various immune and homeostatic functions. Recently, we have described type-1 and type-2 human monocyte-derived Mphi subsets. Although both support outgrowth of intracellular mycobacteria, Mphi-1 secretes interleukin (IL)-23/IL-12 and supports T helper cell type 1 (Th1) responses, whereas Mphi-2 fails to produce IL-23/IL-12, predominantly secretes IL-10, and inhibits Th1 function. Here, we further describe the phenotypic and functional profiles of Mphi-1 and Mphi-2 in response to microbial antigens and interferon-gamma (IFN-gamma) and CD40L as costimulatory T cell back-talk signals. Activated IL-23(+)/IL-12(+) Mphi-1 secreted IL-1beta, IL-18, IL-6, and tumor necrosis factor-alpha (TNF-alpha), as well as IL-8, monocyte chemoattractant protein-1 (MCP-1), IFN-inducible protein 10 (IP-10), Mphi inflammatory protein-1beta (MIP-1beta), regulated on activation, normal T expressed and secreted (RANTES), Mphi-derived chemokine (MDC), and (low levels of) pulmonary and activation-regulated chemokine and thymus and activation-regulated chemokine (TARC), corroborating their proinflammatory function. Regardless of the stimulus, Mphi-2 maintained their IL-10(+) signature cytokine profile and produced no or relatively low levels of IL-12p40, IL-1beta, IL-6, TNF-alpha, MDC, or TARC. It is remarkable that Mphi-2 secreted high levels of IL-8, MCP-1, IP-10, MIP-1beta, and RANTES, suggesting an active role for these cells in regulating cellular immunity and homeostasis. Mphi-1 and Mphi-2 expressed similar levels of Toll-like receptor and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as microbial pattern recognition receptors. Mphi-2, unlike Mphi-1 but like other nonclassical Mphi described previously, expressed CD163 and down-modulated human leukocyte antigen and costimulatory molecules specifically upon activation. These findings demonstrate how Mphi-1/Mphi-2 polarization can differentially skew the host response toward pro- or anti-inflammatory immune responses, respectively. This is likely to be relevant for host-pathogen interactions in chronic bacterial infections and provides a model for dissecting pro- and anti-inflammatory cascades. FAU - Verreck, Frank A W AU - Verreck FA AD - LUMC, Albinusdreef 2, Leiden NL-2333-ZA, The Netherlands. FAU - de Boer, Tjitske AU - de Boer T FAU - Langenberg, Dennis M L AU - Langenberg DM FAU - van der Zanden, Linda AU - van der Zanden L FAU - Ottenhoff, Tom H M AU - Ottenhoff TH LA - eng PT - Comparative Study PT - Journal Article DEP - 20051205 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Antigens, Bacterial) RN - 0 (Biomarkers) RN - 0 (Chemokines) RN - 0 (Interleukins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 147205-72-9 (CD40 Ligand) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antigens, Bacterial/*pharmacology MH - Biomarkers/metabolism MH - CD40 Ligand/*physiology MH - Cell Differentiation/drug effects/immunology MH - Cell Polarity/drug effects/immunology MH - Chemokines/metabolism MH - Humans MH - Immunophenotyping MH - Interferon-gamma/*pharmacology MH - Interleukins/metabolism MH - Macrophages/*classification/drug effects/*immunology MH - Monocytes/drug effects/immunology MH - Phenotype MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2005/12/07 09:00 MHDA- 2006/05/12 09:00 CRDT- 2005/12/07 09:00 PHST- 2005/12/07 09:00 [pubmed] PHST- 2006/05/12 09:00 [medline] PHST- 2005/12/07 09:00 [entrez] AID - jlb.0105015 [pii] AID - 10.1189/jlb.0105015 [doi] PST - ppublish SO - J Leukoc Biol. 2006 Feb;79(2):285-93. doi: 10.1189/jlb.0105015. Epub 2005 Dec 5.