Table 1.
General Characteristics of Lung Monocytic Cell Subsets.
| Mononuclear cell subset | Transcription factor | Secretory profile | Functional role |
|---|---|---|---|
| Alveolar macrophages (SiglecF + CD11c + CD11b − CD71+) | |||
| Unprimed alveolar macrophages | PPARγ, STAT6, STAT3, FOXP3, SOCS3 [20] | Immunosuppressive prostaglandins, TGFβ, GMCSF, retinoic acid, IL10 | Lung microenvironment maintenance; Debris phagocytosis, surfactant turnover. Low antigen presenting activity, suppression of T cell activation [1,21] |
| CD206+CD14+CD169+ | |||
| M1-like alveolar macrophages | STAT1, NFκB, IRF3,7 9 [22] | IFN I, IL6, TNFα, IL1β, IL8, MCP1, MIP1β, IP10, CCL5,CXCL1 | Anti-pathogen defense, acute inflammation and immunoregulation; Attraction of cytotoxic T cells, T helper cells, B-lymphocytes [1,23] |
| CD40+CD80+CD86+ | |||
| M2-like alveolar macrophages | PPARγ, STAT6, STAT3, KLF4, c-MYC, IRF4 [22,24,25] | Arg1, MRC1, CCL17, CCL18, IL10, TGFβ | Alveolar formation in embryogenesis |
| CD71+ CD206+ RELMα + CD163 | Regulatory T cell infiltration, resolution of inflammation; lung tissue reorganization and regeneration [26] | ||
| Interstitial macrophages (SiglecF − CD11b+HLADR + CD71low) | |||
| Unprimed interstitial macrophages | PPARγ, Maf, Maf B, HIF1 [4,5] | IL7, IL10low, IL6, IL4, TNFα, CCL3, CCL4, CCL6−9, CXCL13−14, CCR1, CCR2, IFNA, IFNG | Lung immune homeostasis |
| CD11b + CD11c + CD14+ | Relatively high antigen presenting activity [4,9,10] | ||
| M1-like interstitial macrophages CD206- | STAT1, NFκB, IRF3 | PTX3, IL-12, CXCL13, CCL5, CXCL1,2,9−11, IL11, IL33 | Th1 cell activation |
| T and B lymphocyte chemoattraction | |||
| Phagocytosis [6,27] | |||
| M2-like interstitial macrophages CD206+ | STAT6 | IL10 high, IL1-Ra, CXCL11, CXCL10, CXCL9, CXCL2, CCL12 [6] | Immunoregulation,lung tissue reorganization and regeneration [6,28] |
| STAT3 | |||
| KLF4 | |||
| Blood-derived monocytes CD14+ CD16+/- CCR + CCR5+ CD62L+ | |||
| Unprimed monocytes CD80+CD163+(CD14++CD16-CCR2+ classical, CD14dimCD16++CX3CR1+ | Irf8, Klf2, Klf4, C/EBPβ, Nur77 [31,32] | IL1β low, IL6, TNFα, CCL2, CCR2, CCL24 [33] | Blood homeostasis |
| Non-classical, CD14++CD16 + C × 3CR1+(intermediate) [29][30] | Maintenance of macrophage and dendritic cell populations [34] | ||
| M1-like monocytes/macrophages | STAT1, STAT2,NFκB, IRF1,3,5 [37] | IL6, IL1β, IL8, TNFα, MCP1, MCP3, MIP1β, IP10, GMCSF, CXCL10, GBP1 [38] | Acute inflammation |
| CD14+ CD16+/- HLADR + CD80+ CD163- (predominantly from classical monocytes) [29,35,36] | CD8+ T cell attraction | ||
| Reactive oxygen species production | |||
| Pro-inflammatory activity during late stages of pneumonia | |||
| Maintenance of dendritic cell pool [30,39,40,41] | |||
| M2-like monocytes/macrophages | STAT6, STAT3, KLF4, IRF4 [44] | IL10, CXCL2 (MIP2), Arg1, IL1ra [45] | Immunoregulatory activity |
| CD14DIM CD16- CD80- CD163+(predominantly from non-classical monocytes) [29,42,43] | Alveolar epithelium restoration | ||
| Lung tissue reorganization and regeneration | |||
| Fibrosis [28,45,46] | |||