The lung as an organ that is fully exposed to the external environment for extended periods, comes into contact with numerous inhaled microorganisms. Lung macrophages are crucial for maintaining lung immunity and operate primarily through signaling pathways such as toll-like receptor 4 and nuclear factor-κB pathways. These macrophages constitute a diverse population with significant plasticity, exhibiting different phenotypes and functions on the basis of their origin, tissue residence, and environmental factors. During lung homeostasis, they are involved in the clearance of inhaled particles, cellular remnants, and even participate in metabolic processes. In disease states, lung macrophages transition from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. These distinct phenotypes have varying transcriptional profiles and serve different functions, from combating pathogens to repairing inflammation-induced damage. However, macrophages can also exacerbate lung injury during prolonged inflammation or exposure to antigens. In this review, we delve into the diverse roles of pulmonary macrophages the realms in homeostasis, pneumonia, tuberculosis, and lung tumors.
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References
1.
AegerterH, LambrechtBN, JakubzickCV. Biology of lung macrophages in health and disease. Immunity, 2022; 55(9):1564–1580.
2.
AhmadF, RaniA, AlamA, et al.Macrophage: A cell with many faces and functions in tuberculosis. Front Immunol, 2022; 13:747799.
3.
AllardB, PanaritiA, MartinJG. Alveolar macrophages in the resolution of inflammation, tissue repair, and tolerance to infection. Front Immunol, 2018; 9:1777.
4.
AlysandratosKD, HerrigesMJ, KottonDN. Epithelial stem and progenitor cells in lung repair and regeneration. Annu Rev Physiol, 2021; 83:529–550.
5.
AtriC, GuerfaliFZ, LaouiniD. Role of human macrophage polarization in inflammation during infectious diseases. Int J Mol Sci, 2018; 19.
6.
BeizaviZ, ZohouriM, AsadipourM, et al.IL-27, a pleiotropic cytokine for fine-tuning the immune response in cancer. Int Rev Immunol, 2021; 40(5):319–329.
7.
BertoliniTB, DE SouzaAI, GembreAF, et al.Genetic background affects the expansion of macrophage subsets in the lungs of Mycobacterium tuberculosis-infected hosts. Immunology, 2016; 148(1):102–113.
8.
BickettTE, KaramSD. Tuberculosis-cancer parallels in immune response regulation. Int J Mol Sci, 2020; 21(17).
9.
BlériotC, ChakarovS, GinhouxF. Determinants of resident tissue macrophage identity and function. Immunity, 2020; 52(6):957–970.
10.
BoutilierAJ, ElsawaSF. Macrophage polarization states in the tumor microenvironment. Int J Mol Sci, 2021; 22(13).
11.
CarranzaC, Chavez-GalanL. Several routes to the same destination: Inhibition of Phagosome-Lysosome fusion by mycobacterium tuberculosis. Am J Med Sci, 2019; 357(3):184–194.
12.
Carreira-SantosS, López-SejasN, González-SánchezM, et al.Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function. Front Immunol, 2023; 14:1256404.
13.
ChatterjeeS, YabajiSM, RukhlenkoOS, et al.Channeling macrophage polarization by rocaglates increases macrophage resistance to Mycobacterium tuberculosis. iScience, 2021; 24(8):102845.
14.
ChenX, DuY, HuangZ. CD4+CD25+ treg derived from hepatocellular carcinoma mice inhibits tumor immunity. Immunol Lett, 2012b;148(1):83–89.
15.
ChengP, LiS, ChenH. Macrophages in lung injury, repair, and fibrosis. Cells, 2021; 10(2).
16.
ChenX, LiuY, GaoY, et al.The roles of macrophage polarization in the host immune response to sepsis. Int Immunopharmacol, 2021; 96:107791.
17.
ChenC, ZhuYB, ShenY, et al.Increase of circulating B7-H4-expressing CD68+ macrophage correlated with clinical stage of lung carcinomas. J Immunother, 2012a;35(4):354–358.
18.
CiesielskaA, MatyjekM, KwiatkowskaK. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol Life Sci, 2021; 78(4):1233–1261.
19.
CohenSB, GernBH, DelahayeJL, et al.Alveolar macrophages provide an early mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe, 2018; 24(3):439–446.e4.
20.
CoillardA, SeguraE. In vivo differentiation of human monocytes. Front Immunol, 2019; 10:1907.
21.
CosoS, ZengY, OpeskinK, et al.Vascular endothelial growth factor receptor-3 directly interacts with phosphatidylinositol 3-kinase to regulate lymphangiogenesis. PLoS One, 2012; 7(6):e39558.
22.
DallavalasaS, BeerakaNM, BasavarajuCG, et al.The role of tumor associated macrophages (TAMs) in cancer progression, chemoresistance, angiogenesis and metastasis - current status. Curr Med Chem, 2021; 28(39):8203–8236.
23.
DevA, IyerS, RazaniB, et al.NF-κB and innate immunity. Curr Top Microbiol Immunol, 2011; 349:115–143.
24.
DingM, FeiY, ZhuJ, et al.IL-27 improves adoptive CD8(+) T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation. Cancer Sci, 2022; 113(7):2258–2271.
25.
DorringtonMG, FraserIDC. NF-κB signaling in macrophages: Dynamics, crosstalk, and signal integration. Front Immunol, 2019; 10:705.
26.
Du CheyneC, TayH, DE SpiegelaereW. The complex TIE between macrophages and angiogenesis. Anat Histol Embryol, 2020; 49(5):585–596.
27.
DukhinovaM, KokinosE, KuchurP, et al.Macrophage-derived cytokines in pneumonia: Linking cellular immunology and genetics. Cytokine Growth Factor Rev, 2021; 59:46–61.
28.
FanEKY, FanJ. Regulation of alveolar macrophage death in acute lung inflammation. Respir Res, 2018; 19(1):50.
29.
FengR, ChenY, LiuY, et al.The role of B7-H3 in tumors and its potential in clinical application. Int Immunopharmacol, 2021; 101(Pt B):108153.
30.
FremondCM, TogbeD, DozE, et al.IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J Immunol, 2007; 179(2):1178–1189.
31.
FuLQ, DuWL, CaiMH, et al.The roles of tumor-associated macrophages in tumor angiogenesis and metastasis. Cell Immunol, 2020; 353:104119.
32.
FujitaT, EndoM, GuY, et al.Mycobacterium tuberculosis infection in cancer patients at a tertiary care cancer center in Japan. J Infect Chemother, 2014; 20(3):213–216.
33.
FujiwaraN, KobayashiK. Macrophages in inflammation. Curr Drug Targets Inflamm Allergy, 2005; 4(3):281–286.
34.
FuHY, LiC, YangW, et al.FOXP3 and TLR4 protein expression are correlated in non-small cell lung cancer: Implications for tumor progression and escape. Acta Histochem, 2013; 115(2):151–157.
35.
GaoH, WenN, XuX, et al.[Endoplasmic reticulum stress enhances tumor necrosis factor-α expression in rat kupffer cells to trigger hepatic stellate apoptosis cell through TNFR/caspase-8 pathway]. Nan Fang Yi Ke Da Xue Xue Bao, 2020; 40(5):632–639.
36.
GaoS, ZhouJ, LiuN, et al.Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13. J Mol Cell Cardiol, 2015; 85:131–139.
37.
GarbiN, LambrechtBN. Location, function, and ontogeny of pulmonary macrophages during the steady state. Pflugers Arch, 2017; 469(3–4):561–572.
38.
GermannT, RüDEE. Interleukin-12. Int Arch Allergy Immunol, 1995; 108(2):103–112.
39.
GianchecchiE, FierabracciA. Inhibitory receptors and pathways of lymphocytes: The role of PD-1 in treg development and their involvement in autoimmunity onset and cancer progression. Front Immunol, 2018; 9:2374.
40.
Gomez PerdigueroE, KlapprothK, SchulzC, et al.Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature, 2015; 518(7540):547–551.
41.
GoswamiKK, BoseA, BaralR. Macrophages in tumor: An inflammatory perspective. Clin Immunol, 2021; 232:108875.
42.
GrigoriadisG, ZhanY, GrumontRJ, et al.The rel subunit of NF-kappaB-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for rel in different macrophage populations. Embo J, 1996; 15(24):7099–7107.
43.
GuanX. Cancer metastases: Challenges and opportunities. Acta Pharm Sin B, 2015; 5(5):402–418.
44.
GuerrieroJL. Macrophages: Their untold story in T cell activation and function. Int Rev Cell Mol Biol, 2019; 342:73–93.
45.
GüNEY EskilerG, Deveci ÖzkanA, KaleliS, et al.Inhibition of TLR4/TRIF/IRF3 signaling pathway by curcumin in breast cancer cells. J Pharm Pharm Sci, 2019; 22(1):281–291.
46.
GuoL, ZhaoJ, QuY, et al.microRNA-20a inhibits autophagic process by targeting ATG7 and ATG16L1 and favors mycobacterial survival in macrophage cells. Front Cell Infect Microbiol, 2016; 6:134.
47.
HaydenMS, GhoshS. NF-κB in immunobiology. Cell Res, 2011; 21(2):223–244.
48.
HayesMP, WangJ, NorcrossMA. Regulation of interleukin-12 expression in human monocytes: Selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes. Blood, 1995; 86(2):646–650.
49.
HOPPSTäDTERJ, DieselB, ZarbockR, et al.Differential cell reaction upon toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages. Respir Res, 2010; 11(1):124.
50.
HuangX, CaoM, XiaoY. Alveolar macrophages in pulmonary alveolar proteinosis: Origin, function, and therapeutic strategies. Front Immunol, 2023; 14:1195988.
51.
HuangJ, ChenY, ZhouL, et al.M2a macrophages regulate fibrosis and affect the outcome after stroke via PU.1/mTOR pathway in fibroblasts. Neurochem Int, 2024; 173:105674.
52.
HuangD, WangP, ChenJ, et al.Selective targeting of MD2 attenuates intestinal inflammation and prevents neonatal necrotizing enterocolitis by suppressing TLR4 signaling. Front Immunol, 2022; 13:995791.
53.
HuangH, WangX, ZhangY, et al.Up-regulation of NKG2F receptor, a functionally unknown killer receptor, of human natural killer cells by interleukin-2 and interleukin-15. Oncol Rep, 2010; 24(4):1043–1048.
54.
HuY, CongX, ChenL, et al.Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway. Sci Rep, 2016; 6:23977.
55.
HuX, GuY, ZhaoS, et al.Elevated circulating CD4(+)CD25(−)Foxp3(+) regulatory T cells in patients with nonsmall cell lung cancer. Cancer Biother Radiopharm, 2019; 34(5):325–333.
56.
JagtapP, PrasadP, PateriaA, et al.A single step in vitro bioassay mimicking TLR4-LPS pathway and the role of MD2 and CD14 coreceptors. Front Immunol, 2020; 11:5.
57.
JiaT, FuH, SunJ, et al.Foxp3 expression in A549 cells is regulated by toll-like receptor 4 through nuclear factor-κB. Mol Med Rep, 2012; 6(1):167–172.
58.
JiangM, WangD, SuN, et al.TRIM65 knockout inhibits the development of HCC by polarization tumor-associated macrophages towards M1 phenotype via JAK1/STAT1 signaling pathway. Int Immunopharmacol, 2024; 128:111494.
59.
KaneganeC, SgadariC, KaneganeH, et al.Contribution of the CXC chemokines IP-10 and mig to the antitumor effects of IL-12. J Leukoc Biol, 1998; 64(3):384–392.
60.
KangIS, KimRI, KimC. Carbon monoxide regulates macrophage differentiation and polarization toward the M2 phenotype through upregulation of heme oxygenase 1. Cells, 2021; 10(12).
61.
KashfiK, KannikalJ, NathN. Macrophage reprogramming and cancer therapeutics: Role of iNOS-derived NO. Cells, 2021; 10(11).
62.
KawaiT, AkiraS. TLR signaling. Cell Death Differ, 2006; 13(5):816–825.
KimYK, KimSE, Chang ParkH, et al.Human recombinant IL-10 reduces xenogenic cytotoxicity via macrophage M2 polarization. Biochem Biophys Rep, 2020; 24:100857.
65.
KimuraH, SuzukiM, KonnoS, et al.Orchestrating role of apoptosis inhibitor of macrophage in the resolution of acute lung injury. J Immunol, 2017; 199(11):3870–3882.
66.
KleinsteuberK, HeeschK, SchattlingS, et al.Decreased expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T cells and peripheral blood from tuberculosis patients. PLoS One, 2013; 8(4):e61609.
67.
KrishnanV, NathS, NairP, et al.Mycobacterium tuberculosis and its clever approaches to escape the deadly macrophage. World J Microbiol Biotechnol, 2023; 39(11):300.
68.
KumarS, MeenaR, PaulrajR. Role of macrophage (M1 and M2) in Titanium-Dioxide nanoparticle-induced oxidative stress and inflammatory response in rat. Appl Biochem Biotechnol, 2016; 180(7):1257–1275.
69.
LandoniE, WoodcockMG, BarraganG, et al.IL-12 reprograms CAR-expressing natural killer T cells to long-lived Th1-polarized cells with potent antitumor activity. Nat Commun, 2024; 15(1):89.
70.
LawrenceT. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol, 2009; 1(6):a001651.
71.
LeJ, KulatheepanY, JeyaseelanS. Role of toll-like receptors and nod-like receptors in acute lung infection. Front Immunol, 2023; 14:1249098.
72.
LechnerAJ, DriverIH, LeeJ, et al.Recruited monocytes and type 2 immunity promote lung regeneration following pneumonectomy. Cell Stem Cell, 2017; 21(1):120–134.e7.
73.
LeeJW, ChunW, LeeHJ, et al.The role of macrophages in the development of acute and chronic inflammatory lung diseases. Cells, 2021; 10(4).
74.
LeemansJC, ThepenT, WeijerS, et al.Macrophages play a dual role during pulmonary tuberculosis in mice. J Infect Dis, 2005; 191(1):65–74.
75.
LinB, Williams-SkippC, TaoY, et al.NF-kappaB functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type. Cell Death Differ, 1999; 6(6):570–582.
76.
LitvakV, RamseySA, RustAG, et al.Function of C/EBPdelta in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals. Nat Immunol, 2009; 10(4):437–443.
77.
LiuJ, GengX, HouJ, et al.New insights into M1/M2 macrophages: Key modulators in cancer progression. Cancer Cell Int, 2021; 21(1):389.
78.
LiuH, GuiX, ChenS, et al.Structural variability of lipoarabinomannan modulates innate immune responses within infected alveolar epithelial cells. Cells, 2022a;11(3).
79.
LiuG, LuY, ShiL, et al.TLR4-MyD88 signaling pathway is responsible for acute lung inflammation induced by reclaimed water. J Hazard Mater, 2020; 396:122586.
80.
LiuL, StokesJV, TanW, et al.An optimized flow cytometry panel for classifying macrophage polarization. J Immunol Methods, 2022b;511:113378.
81.
LiuC, XieC, LinY, et al.IL-12 induces autophagy via AKT/mTOR/STAT3 signaling pathway in human hepatoma cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2016[;32:870–875.
82.
LocatiM, CurtaleG, MantovaniA. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol, 2020; 15:123–147.
83.
LoosP, MarichalT, MachielsB, et al.Differentiation of bone marrow monocytes into alveolar macrophages-like cells through Co-culture with lung epithelial cells and group 2 innate lymphoid cells. Bio Protoc, 2023; 13(18):e4818.
84.
LuY, HanG, ZhangY, et al.M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma. Cell Commun Signal, 2023; 21(1):299.
85.
LuYC, YehWC, OhashiPS. LPS/TLR4 signal transduction pathway. Cytokine, 2008; 42(2):145–151.
86.
MeloEM, OliveiraVLS, BoffD, et al.Pulmonary macrophages and their different roles in health and disease. Int J Biochem Cell Biol, 2021; 141:106095.
87.
MiraghazadehB, CookMC. Nuclear factor-kappaB in autoimmunity: Man and mouse. Front Immunol, 2018; 9:613.
88.
Molina-RomeroC, ArrietaO, HERNáNDEZ-PandoR. Tuberculosis and lung cancer. Salud Publica Mex, 2019; 61(3):286–291.
89.
MuG, ZhuY, DongZ, et al.Calmodulin 2 facilitates angiogenesis and metastasis of gastric cancer via STAT3/HIF-1A/VEGF-A mediated macrophage polarization. Front Oncol, 2021; 11:727306.
90.
MuleroMC, HuxfordT, GhoshG. NF-κB, IκB, and IKK: Integral components of immune system signaling. Adv Exp Med Biol, 2019; 1172:207–226.
91.
MussbacherM, DerlerM, BASíLIOJ, et al.NF-κB in monocytes and macrophages—an inflammatory master regulator in multitalented immune cells. Front Immunol, 2023; 14:1134661.
92.
MuxelSM, Pires-LapaMA, MonteiroAW, et al.NF-κB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-N-acetyltransferase (AA-NAT) gene. PLoS One, 2012; 7(12):e52010.
93.
MwebazaI, ShawR, LiQ, et al.Impact of Mycobacterium tuberculosis glycolipids on the CD4+ T Cell-Macrophage immunological synapse. J Immunol, 2023; 211(9):1385–1396.
94.
NaeemMA, AhmadW, TyagiR, et al.Stealth strategies of Mycobacterium tuberculosis for immune evasion. Curr Issues Mol Biol, 2021; 41:597–616.
95.
NalbandianA, YanBS, PichuginA, et al.Lung carcinogenesis induced by chronic tuberculosis infection: The experimental model and genetic control. Oncogene, 2009; 28(17):1928–1938.
96.
NapetschnigJ, WuH. Molecular basis of NF-κB signaling. Annu Rev Biophys, 2013; 42:443–468.
97.
NicodLP, JoudrierS, IslerP, et al.Upregulation of CD40, CD80, CD83 or CD86 on alveolar macrophages after lung transplantation. J Heart Lung Transplant, 2005; 24(8):1067–1075.
98.
O’neillLA, BowieAG. The family of five: TIR-domain-containing adaptors in toll-like receptor signalling. Nat Rev Immunol, 2007; 7(5):353–364.
99.
PanY, YuY, WangX, et al.Tumor-Associated macrophages in tumor immunity. Front Immunol, 2020; 11:583084.
100.
ParkWH. MAPK inhibitors, particularly the JNK inhibitor, increase cell death effects in H2O2-treated lung cancer cells via increased superoxide anion and glutathione depletion. Oncol Rep, 2018; 39(2):860–870.
101.
ParkMD, SilvinA, GinhouxF, et al.Macrophages in health and disease. Cell, 2022; 185(23):4259–4279.
102.
ParkR, YuJ, ShahzadM, et al.The immune regulatory function of B7-H3 in malignancy: Spotlight on the IFN-STAT1 axis and regulation of tumor-associated macrophages. Immunol Res, 2024; 72(4):881.
103.
PereiraM, DursoDF, BryantCE, et al.The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways. Cell Rep, 2022; 40(7):111225.
104.
PoorTA, Morales-NebredaL. Alveolar macrophages during inflammation: A balancing act. Am J Respir Cell Mol Biol, 2023; 68(6):608–609.
RameshP, ShivdeR, JaishankarD, et al.A palette of cytokines to measure anti-tumor efficacy of T Cell-Based therapeutics. Cancers (Basel), 2021; 13(4).
107.
RaslanAA, YoonJK. WNT signaling in lung repair and regeneration. Mol Cells, 2020; 43(9):774–783.
108.
RathM, MüLLERI, KropfP, et al.Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Front Immunol, 2014; 5:532.
109.
RenS, ZhangX, HuY, et al.Blocking the notch signal transduction pathway promotes tumor growth in osteosarcoma by affecting polarization of TAM to M2 phenotype. Ann Transl Med, 2020; 8(17):1057.
110.
Richard-GreenblattM, Av-GayY. Epigenetic phosphorylation control of Mycobacterium tuberculosis infection and persistence. Microbiol Spectr, 2017; 5(2).
111.
RodriguezGM, SharmaN, BiswasA, et al.The iron response of Mycobacterium tuberculosis and its implications for tuberculosis pathogenesis and novel therapeutics. Front Cell Infect Microbiol, 2022; 12:876667.
112.
RossolM, HeineH, MeuschU, et al.LPS-induced cytokine production in human monocytes and macrophages. Crit Rev Immunol, 2011; 31(5):379–446.
113.
RoyD, EhteshamNZ, HasnainSE. Is Mycobacterium tuberculosis carcinogenic to humans? Faseb J, 2021; 35(9):e21853.
114.
Sandoval-BorregoD, Moreno-LafontMC, Vazquez-SanchezEA, et al.Overexpression of CD158 and NKG2A inhibitory receptors and underexpression of NKG2D and NKp46 activating receptors on NK cells in acute myeloid leukemia. Arch Med Res, 2016; 47(1):55–64.
115.
SanjabiS, HoffmannA, LiouHC, et al.Selective requirement for c-rel during IL-12 P40 gene induction in macrophages. Proc Natl Acad Sci U S A, 2000; 97(23):12705–12710.
116.
SantoniM, MassariF, AmantiniC, et al.Emerging role of tumor-associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother, 2013; 62(12):1757–1768.
117.
SasakiY, IwaiK. Roles of the NF-κB pathway in B-Lymphocyte biology. Curr Top Microbiol Immunol, 2016; 393:177–209.
118.
ScheragaRG, SouthernBD, GroveLM, et al.The role of TRPV4 in regulating innate immune cell function in lung inflammation. Front Immunol, 2020; 11:1211.
119.
SCHRöDERNW, SchumannRR. Non-LPS targets and actions of LPS binding protein (LBP). J Endotoxin Res, 2005; 11(4):237–242.
SedighzadehSS, KhoshbinAP, RaziS, et al.A narrative review of tumor-associated macrophages in lung cancer: Regulation of macrophage polarization and therapeutic implications. Transl Lung Cancer Res, 2021; 10(4):1889–1916.
122.
SgadariC, AngiolilloAL, TosatoG. Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10. Blood, 1996; 87(9):3877–3882.
123.
ShenJ, ChiP, ZhangF, et al.[IL-12 contributes to reconstruction of cellular immune function of tumor patients and mice after chemotherapeutics]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2018; 34(4):289–295.
124.
ShenX, SunC, ChengY, et al.cGAS mediates inflammation by polarizing macrophages to M1 phenotype via the mTORC1 pathway. J Immunol, 2023; 210(8):1098–1107.
125.
ShiT, DenneyL, AnH, et al.Alveolar and lung interstitial macrophages: Definitions, functions, and roles in lung fibrosis. J Leukoc Biol, 2021; 110(1):107–114.
126.
ShinDM, JeonBY, LeeHM, et al.Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling. PLoS Pathog, 2010; 6(12):e1001230.
127.
StennickeHR, JürgensmeierJM, ShinH, et al.Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem, 1998; 273:27084–27090.
128.
StrizovaZ, BenesovaI, BartoliniR, et al.M1/M2 macrophages and their overlaps—myth or reality? Clin Sci (Lond), 2023; 137(15):1067–1093.
129.
SunSC. The noncanonical NF-κB pathway. Immunol Rev, 2012; 246(1):125–140.
130.
SunZ, XuY, ShaoB, et al.Exosomal circPOLQ promotes macrophage M2 polarization via activating IL-10/STAT3 axis in a colorectal cancer model. J Immunother Cancer, 2024; 12(5).
TakeuchiO, AkiraS. Toll-like receptors; their physiological role and signal transduction system. Int Immunopharmacol, 2001; 1(4):625–635.
134.
TangS, NingQ, YangL, et al.Mechanisms of immune escape in the cancer immune cycle. Int Immunopharmacol, 2020; 86:106700.
135.
TangL, ZhangH, WangC, et al.M2A and M2C macrophage subsets ameliorate inflammation and fibroproliferation in acute lung injury through interleukin 10 pathway. Shock, 2017; 48(1):119–129.
136.
TorrellesJB, SchlesingerLS. Diversity in Mycobacterium tuberculosis mannosylated cell wall determinants impacts adaptation to the host. Tuberculosis (Edinb), 2010; 90(2):84–93.
137.
TsuchiyaK, SuzukiY, YoshimuraK, et al.Macrophage mannose receptor CD206 predicts prognosis in community-acquired pneumonia. Sci Rep, 2019; 9(1):18750.
138.
VannellaKM, WynnTA. Mechanisms of organ injury and repair by macrophages. Annu Rev Physiol, 2017; 79:593–617.
139.
VerzellaD, PescatoreA, CapeceD, et al.Life, death, and autophagy in cancer: NF-κB turns up everywhere. Cell Death Dis, 2020; 11(3):210.
140.
VoisinA, Grinberg-BleyerY. The many-sided contributions of NF-κB to T-cell biology in health and disease. Int Rev Cell Mol Biol, 2021; 361:245–300.
141.
WangJ, HuangH, LuJ, et al.Tumor cells induced-M2 macrophage favors accumulation of treg in nasopharyngeal carcinoma. Int J Clin Exp Pathol, 2017; 10(8):8389–8401.
142.
WangS, LiuG, LiY, et al.Metabolic reprogramming induces macrophage polarization in the tumor microenvironment. Front Immunol, 2022a;13:840029.
143.
WangQ, NiH, LanL, et al.Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages. Cell Res, 2010; 20(6):701–712.
144.
WangL, ShangX, QiX, et al.Clinical significance of M1/M2 macrophages and related cytokines in patients with spinal tuberculosis. Dis Markers, 2020a;2020:2509454.
145.
WangZ, WangZ. The role of macrophages polarization in sepsis-induced acute lung injury. Front Immunol, 2023; 14:1209438.
146.
WangX, WuY, GuJ, et al.Tumor-associated macrophages in lung carcinoma: From mechanism to therapy. Pathol Res Pract, 2022b;229:153747.
147.
WangWM, XuXS, MiaoCM. Kupffer Cell-Derived TNF-α triggers the apoptosis of hepatic stellate cells through TNF-R1/caspase 8 due to ER stress. Biomed Res Int, 2020b;2020:8035671.
148.
WangX, YuW, LiH, et al.Can the dual-functional capability of CIK cells be used to improve antitumor effects? Cell Immunol, 2014; 287:18–22.
149.
WangLX, ZhangSX, WuHJ, et al.M2b macrophage polarization and its roles in diseases. J Leukoc Biol, 2019; 106(2):345–358.
150.
WeidenM, TanakaN, QiaoY, et al.Differentiation of monocytes to macrophages switches the Mycobacterium tuberculosis effect on HIV-1 replication from stimulation to inhibition: Modulation of interferon response and CCAAT/enhancer binding protein beta expression. J Immunol, 2000; 165(4):2028–2039.
151.
WinklerJ, Abisoye-OgunniyanA, MetcalfKJ, et al.Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun, 2020; 11(1):5120.
152.
WongKW. The role of ESX-1 in Mycobacterium tuberculosis pathogenesis. Microbiol Spectr, 2017; 5(3).
153.
WooYD, JeongD, ChungDH. Development and functions of alveolar macrophages. Mol Cells, 2021; 44(5):292–300.
154.
XiongK, SunW, HeY, et al.Advances in molecular mechanisms of interaction between Mycobacterium tuberculosis and lung cancer: A narrative review. Transl Lung Cancer Res, 2021; 10(10):4012–4026.
155.
XuM, MizoguchiI, MorishimaN, et al.Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27. Clin Dev Immunol, 2010; 2010.
YamamotoM, SatoS, HemmiH, et al.Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science, 2003; 301(5633):640–643.
158.
YangL, DongY, LiY, et al.IL-10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF-κB/Notch1 pathway in non-small cell lung cancer. Int J Cancer, 2019; 145(4):1099–1110.
159.
YangQ, GuoN, ZhouY, et al.The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. Acta Pharm Sin B, 2020; 10(11):2156–2170.
160.
YangCK, HuangCH, HuCH, et al.Immunophenotype and antitumor activity of cytokine-induced killer cells from patients with hepatocellular carcinoma. PLoS One, 2023; 18(1):e0280023.
161.
YangZ, SunD, YanZ, et al.Differential role for p120-catenin in regulation of TLR4 signaling in macrophages. J Immunol, 2014; 193(4):1931–1941.
162.
YuanL, YeJ, FanD. The B7-H4 gene induces immune escape partly via upregulating the PD-1/Stat3 pathway in non-small cell lung cancer. Hum Immunol, 2020; 81(5):254–261.
163.
YuX, ButtgereitA, LeliosI, et al.The cytokine TGF-β promotes the development and homeostasis of alveolar macrophages. Immunity, 2017; 47(5):903–912.e4.
164.
YuZ, TangH, ChenS, et al.Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist Updat, 2023; 67:100915.
165.
ZachariasWJ, FrankDB, ZeppJA, et al.Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor. Nature, 2018; 555(7695):251–255.
166.
ZhangW, DongC, XiongS. Mycobacterial SapM hampers host autophagy initiation for intracellular bacillary survival via dephosphorylating raptor. iScience, 2024b;27(5):109671.
167.
ZhangH, HeF, LiP, et al.The role of innate immunity in pulmonary infections. Biomed Res Int, 2021a;2021:6646071.
168.
ZhangY, LiS, LiuQ, et al.Mycobacterium tuberculosis Heat-Shock protein 16.3 induces macrophage M2 polarization through CCRL2/CX3CR1. Inflammation, 2020; 43(2):487–506.
169.
ZhangH, LiuD, XuQF, et al.Endothelial RSPO3 mediates pulmonary endothelial regeneration by LGR4-dependent activation of β-catenin and ILK signaling pathways after inflammatory vascular injury. Int J Biol Macromol, 2024a;269(Pt 2):131805.
170.
ZhangZQ, TianHT, LiuH, et al.The role of macrophage-derived TGF-β1 on SiO(2)-induced pulmonary fibrosis: A review. Toxicol Ind Health, 2021b;37(4):240–250.
171.
ZhenH, HuH, TanC, et al.Regulation of M1/M2 polarization in LPS-Stimulated macrophages by 1,25(OH)2D3. Altern Ther Health Med, 2023; 29(8):501–505.
172.
ZhouB, MaganaL, HongZ, et al.The angiocrine Rspondin3 instructs interstitial macrophage transition via metabolic-epigenetic reprogramming and resolves inflammatory injury. Nat Immunol, 2020a;21(11):1430–1443.
173.
ZhouJ, TangZ, GaoS, et al.Tumor-Associated macrophages: Recent insights and therapies. Front Oncol, 2020b;10:188.
174.
ZhuP, PuY, WangM, et al.MnOOH-Catalyzed autoxidation of glutathione for reactive oxygen species production and nanocatalytic tumor innate immunotherapy. J Am Chem Soc, 2023; 145(10):5803–5815.
175.
ZhuangH, DaiX, ZhangX, et al.Sophoridine suppresses macrophage-mediated immunosuppression through TLR4/IRF3 pathway and subsequently upregulates CD8(+) T cytotoxic function against gastric cancer. Biomed Pharmacother, 2020; 121:109636.
176.
ZouS, JieH, HanX, et al.The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury. Int Immunopharmacol, 2023; 124(Pt A):110436.
