{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T22:07:14Z","timestamp":1775254034791,"version":"3.50.1"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Latent tuberculosis infection (LTBI) poses a major roadblock in the global effort to eradicate tuberculosis (TB). A deep understanding of the host responses involved in establishment and maintenance of TB latency is required to propel the development of sensitive methods to detect and treat LTBI. Given that LTBI individuals are typically asymptomatic, it is challenging to differentiate latently infected from uninfected individuals. A major contributor to this problem is that no clear pattern of host response is linked with LTBI, as molecular correlates of latent infection have been hard to identify. In this study, we have analyzed the global perturbations in host response in LTBI individuals as compared to uninfected individuals and particularly the heterogeneity in such response, across LTBI cohorts. For this, we constructed individualized genome-wide host response networks informed by blood transcriptomes for 136 LTBI cases and have used a sensitive network mining algorithm to identify top-ranked host response subnetworks in each case. Our analysis indicates that despite the high heterogeneity in the gene expression profiles among LTBI samples, clear patterns of perturbation are found in the immune response pathways, leading to grouping LTBI samples into 4 different immune-subtypes. Our results suggest that different subnetworks of molecular perturbations are associated with latent tuberculosis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.595746","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T14:41:03Z","timestamp":1617806463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Immune Subtyping in Latent Tuberculosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Ushashi","family":"Banerjee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Baloni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagasuma","family":"Chandra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"B1","volume-title":"WHO | Global tuberculosis report 2018","year":"2018"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1038\/emi.2016.10","article-title":"Updates on the risk factors for latent tuberculosis reactivation and their managements","volume":"5","author":"Ai","year":"2016","journal-title":"Emerging Microbes Infections"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.7.4195-4201.2001","article-title":"Tuberculosis: latency and reactivation","volume":"69","author":"Flynn","year":"2001","journal-title":"Infection Immun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/CMR.00021-18","article-title":"Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection","volume":"31","author":"Drain","year":"2018","journal-title":"Clin Microbiol Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir451","article-title":"Incipient and Subclinical Tuberculosis: Defining Early Disease States in the Context of Host Immune Response","volume":"204","author":"Achkar","year":"2011","journal-title":"J Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir068","article-title":"Clinical Application and Limitations of Interferon-Release Assays for the Diagnosis of Latent Tuberculosis Infection","volume":"52","author":"Herrera","year":"2011","journal-title":"Clin Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nature09247","article-title":"An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis","volume":"466","author":"Berry","year":"2010","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041169","article-title":"Global transcriptome analysis in influenza-infected mouse lungs reveals the kinetics of innate and adaptive host immune responses","volume":"7","author":"Pommerenke","year":"2012","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00778-15","article-title":"Simultaneous Host-Pathogen Transcriptome Analysis during Granulibacter bethesdensis Infection of Neutrophils from Healthy Subjects and Patients with Chronic Granulomatous Disease","volume":"83","author":"Greenberg","year":"2015","journal-title":"Infection Immun"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1038\/srep02302","article-title":"Mining large-scale response networks reveals \u2018topmost activities\u2019 in Mycobacterium tuberculosis infection","volume":"3","author":"Sambarey","year":"2013","journal-title":"Sci Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep15214","article-title":"Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection","volume":"5","author":"Maji","year":"2015","journal-title":"Sci Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201707-1475OC","article-title":"B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis","volume":"197","author":"B\u00e9nard","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026938","article-title":"Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis","volume":"6","author":"Maertzdorf","year":"2011","journal-title":"PloS One"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001538","article-title":"Detection of tuberculosis in HIV-infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study","volume":"10","author":"Kaforou","year":"2013","journal-title":"PloS Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)00048-5","article-title":"Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis","volume":"4","author":"Sweeney","year":"2016","journal-title":"Lancet Respir Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02121-2015","article-title":"A 380-gene meta-signature of active tuberculosis compared with healthy controls","volume":"47","author":"Blankley","year":"2016","journal-title":"Eur Respir J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.12.009","article-title":"Unbiased Identification of Blood-based Biomarkers for Pulmonary Tuberculosis by Modeling and Mining Molecular Interaction Networks","volume":"15","author":"Sambarey","year":"2017","journal-title":"EBioMedicine"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01316-1","article-title":"A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet (London","volume":"387","author":"Zak","year":"2016","journal-title":"England)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800118","article-title":"Transcriptomic Analysis of CD4+ T Cells Reveals Novel Immune Signatures of Latent Tuberculosis","volume":"200","author":"Burel","year":"2018","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00457","article-title":"Meta-Analysis Identification of Highly Robust and Differential Immune-Metabolic Signatures of Systemic Host Response to Acute and Latent Tuberculosis in Children and Adults","volume":"9","author":"Bah","year":"2018","journal-title":"Front Genet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41540-017-0005-4","article-title":"Meta-analysis of host response networks identifies a common core in tuberculosis","volume":"3","author":"Sambarey","year":"2017","journal-title":"NPJ Syst Biol Appl"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1038\/s41467-018-04579-w","article-title":"A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection","volume":"9","author":"Singhania","year":"2018","journal-title":"Nat Commun"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0046191","article-title":"Detectable Changes in The Blood Transcriptome Are Present after Two Weeks of Antituberculosis Therapy","volume":"7","author":"Bloom","year":"2012","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.tube.2018.01.002","article-title":"Existing blood transcriptional classifiers accurately discriminate active tuberculosis from latent infection in individuals from south India","volume":"109","author":"Leong","year":"2018","journal-title":"Tuberculosis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with Bioconductor","volume":"12","author":"Huber","year":"2015","journal-title":"Nat Methods"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1752-0509-7-7","article-title":"SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks","volume":"7","author":"Fazekas","year":"2013","journal-title":"BMC Syst Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1204","article-title":"The BioGRID interaction database: 2015 update","volume":"43","author":"Chatr-Aryamontri","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002886","article-title":"Interpretation of genomic variants using a unified biological network approach","volume":"9","author":"Khurana","year":"2013","journal-title":"PloS Comput Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1186\/s12864-016-2792-1","article-title":"EpiTracer - an algorithm for identifying epicenters in condition-specific biological networks","volume":"17","author":"Sambaturu","year":"2016","journal-title":"BMC Genomics"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.100986","article-title":"A Strategic Target Rescues Trimethoprim Sensitivity in Escherichia coli","volume":"23","author":"Bhosle","year":"2020","journal-title":"iScience"},{"key":"B36","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinf"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1147","article-title":"InnateDB: systems biology of innate immunity and beyond\u2013recent updates and continuing curation","volume":"41","author":"Breuer","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1023\/A:1023949509487","article-title":"Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data","volume":"52","author":"Monti","year":"2003","journal-title":"Mach Learn"},{"key":"B39","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1021\/acsinfecdis.6b00004","article-title":"Identifying and Tackling Emergent Vulnerability in Drug-Resistant Mycobacteria","volume":"2","author":"Padiadpu","year":"2016","journal-title":"ACS Infect Dis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00025408","article-title":"Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia","volume":"33","author":"Daniels","year":"2009","journal-title":"Eur Respir J"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.07.31","article-title":"A case of tuberculosis reactivation suspected of cancer progression during oral tyrosine kinase inhibitor treatment in a patient diagnosed as non-small cell lung cancer","volume":"9","author":"Lee","year":"2017","journal-title":"J Thoracic Dis"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201711-2340OC","article-title":"Four-Gene Pan-African Blood Signature Predicts Progression to Tuberculosis","volume":"197","author":"Suliman","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2020.101898","article-title":"Cross-validation of existing signatures and derivation of a novel 29-gene transcriptomic signature predictive of progression to TB in a Brazilian cohort of household contacts of pulmonary TB","volume":"120","author":"Leong","year":"2020","journal-title":"Tuberculosis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.7.4320-4328.2001","article-title":"CD8(+) T cells participate in the memory immune response to Mycobacterium tuberculosis","volume":"69","author":"Serbina","year":"2001","journal-title":"Infection Immun"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5368.1435","article-title":"van Breda\u00a0Vriesman PJ, et\u00a0al. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients","volume":"280","author":"de\u00a0Jong","year":"1998","journal-title":"Sci (New York N.Y.)"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e65","DOI":"10.1136\/jmg.2006.043406","article-title":"A novel X-linked recessive form of Mendelian susceptibility to mycobaterial disease","volume":"44","author":"Bustamante","year":"2007","journal-title":"J Med Genet"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.6938","article-title":"Healthy Individuals That Control a Latent Infection with Mycobacterium tuberculosis Express High Levels of Th1 Cytokines and the IL-4 Antagonist IL-42","volume":"172","author":"Demissie","year":"2004","journal-title":"J Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00791.x","article-title":"Reactivation of tuberculosis is associated with a shift from type 1 to type 2 cytokines","volume":"115","author":"Howard","year":"1999","journal-title":"Clin Exp Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.06.005","article-title":"IL-4 in tuberculosis: implications for vaccine design","volume":"25","author":"Rook","year":"2004","journal-title":"Trends Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1086\/422532","article-title":"Increased Interleukin-4 production by CD8 and gammadelta T cells in health-care workers is associated with the subsequent development of active tuberculosis","volume":"190","author":"Ordway","year":"2004","journal-title":"J Infect Dis"},{"key":"B51","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2174\/187152809787582543","article-title":"TNF-alpha in tuberculosis: a cytokine with a split personality","volume":"8","author":"Mootoo","year":"2009","journal-title":"Inflammation Allergy Drug Targets"},{"key":"B52","article-title":"The role of TNF-alpha in T-cell-mediated inflammation depends on the Th1\/Th2 cytokine balance","volume":"82","author":"Hernandez-Pando","year":"1994","journal-title":"Immunology"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1086\/383317","article-title":"Granulomatous Infectious Diseases Associated with Tumor Necrosis Factor Antagonists","volume":"38","author":"Wallis","year":"2004","journal-title":"Clin Infect Dis"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4046\/trd.2014.76.6.261","article-title":"Diagnosis and Treatment of Latent Tuberculosis Infection due to Initiation of Anti-TNF Therapy","volume":"76","author":"Shim","year":"2014","journal-title":"Tuberculosis Respir Dis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0153289","article-title":"Investigating the Role of TNF and IFN- Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages","volume":"11","author":"Salim","year":"2016","journal-title":"PloS One"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5508.1544","article-title":"Induction of direct antimicrobial activity through mammalian toll-like receptors","volume":"291","author":"Thoma-Uszynski","year":"2001","journal-title":"Sci (New York N.Y.)"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-199588","article-title":"Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response","volume":"26","author":"Byun","year":"2012","journal-title":"FASEB J: Off Publ Fed Am Soc Exp Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2009.10.007","article-title":"Role of TLR2- and TLR4-mediated signaling in Mycobacterium tuberculosis-induced macrophage death","volume":"260","author":"S\u00e1nchez","year":"2010","journal-title":"Cell Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1128\/iai.72.4.2400-2404.2004","article-title":"MyD88-deficient mice display a profound loss in resistance to Mycobacterium tuberculosis associated with partially impaired Th1 cytokine and nitric oxide synthase 2 expression","volume":"72","author":"Scanga","year":"2004","journal-title":"Infection Immun"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2011.02.001","article-title":"Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis","volume":"72","author":"Dalgic","year":"2011","journal-title":"Hum Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-011-8229-7","article-title":"Latent tuberculosis: what the host \u201csees\u201d","volume":"50","author":"Gideon","year":"2011","journal-title":"Immunol Res"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01843","article-title":"Deletion of TGF-1 Increases Bacterial Clearance by Cytotoxic T Cells in a Tuberculosis Granuloma Model","volume":"8","author":"Warsinske","year":"2017","journal-title":"Front Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3412","article-title":"Sterilization of granulomas is common in both active and latent tuberculosis despite extensive within-host variability in bacterial killing","volume":"20","author":"Lin","year":"2014","journal-title":"Nat Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02668.x","article-title":"Inhibition of Mycobacterium tuberculosis-induced signalling by transforming growth factor- in human mononuclear phagocytes","volume":"75","author":"Wu","year":"2012","journal-title":"Scandinavian J Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000839","article-title":"Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen","volume":"6","author":"Jayaswal","year":"2010","journal-title":"PloS Pathog"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00046","article-title":"The Tyrosine Kinase Inhibitor Gefitinib Restricts Mycobacterium tuberculosis Growth through Increased Lysosomal Biogenesis and Modulation of Cytokine Signaling","volume":"3","author":"Sogi","year":"2017","journal-title":"ACS Infect Dis"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.64.8.2917-2922.1996","article-title":"Epidermal growth factor-binding protein in Mycobacterium avium and Mycobacterium tuberculosis: a possible role in the mechanism of infection","volume":"64","author":"Bermudez","year":"1996","journal-title":"Infection Immun"},{"key":"B68","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.mam.2017.11.008","article-title":"PDGF in organ fibrosis","volume":"62","author":"Klinkhammer","year":"2018","journal-title":"Mol Aspects Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.791764","article-title":"Pulmonary fibrosis requires cell-autonomous mesenchymal fibroblast growth factor (FGF) signaling","volume":"292","author":"Guzy","year":"2017","journal-title":"J Biol Chem"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13069-016-0043-3","article-title":"Active transforming growth factor- is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis","volume":"9","author":"DiFazio","year":"2016","journal-title":"Fibrogenesis Tissue Repair"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200509-1534OC","article-title":"Gefitinib prevents bleomycin-induced lung fibrosis in mice","volume":"174","author":"Ishii","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"B72","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1365-2249.1993.tb05975.x","article-title":"Up-regulation of alveolar macrophage platelet-derived growth factor-B (PDGF-B) mRNA by interferon-gamma from Mycobacterium tuberculosis antigen (PPD)-stimulated lymphocytes","volume":"94","author":"Wangoo","year":"1993","journal-title":"Clin Exp Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2597","article-title":"Progression of EGFR-Mutant Lung Adenocarcinoma is Driven By Alveolar Macrophages","volume":"23","author":"Wang","year":"2017","journal-title":"Clin Cancer Res: Off J Am Assoc Cancer Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/srep41240","article-title":"M2 macrophages or IL-33 treatment attenuate ongoing Mycobacterium tuberculosis infection","volume":"7","author":"Pi\u00f1eros","year":"2017","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.595746\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T14:41:09Z","timestamp":1617806469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.595746\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,7]]},"references-count":74,"alternative-id":["10.3389\/fimmu.2021.595746"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.595746","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,7]]},"article-number":"595746"}}