{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:30:24Z","timestamp":1787506224183,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR24443\/MED\/29\/1220\/2017"],"award-info":[{"award-number":["BT\/PR24443\/MED\/29\/1220\/2017"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    It is essential to understand the interactions and relationships between\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) and macrophages during the infection in order to design host-directed, immunomodulation-dependent therapeutics to control\n                    <jats:italic>Mtb<\/jats:italic>\n                    . We had reported previously that ornithine acetyltransferase (MtArgJ), a crucial enzyme of the arginine biosynthesis pathway of\n                    <jats:italic>Mtb<\/jats:italic>\n                    , is allosterically inhibited by pranlukast (PRK), which significantly reduces bacterial growth. The present investigation is centered on the immunomodulation in the host by PRK particularly the activation of the host\u2019s immune response to counteract bacterial survival and pathogenicity. Here, we show that PRK decreased the bacterial burden in the lungs by upregulating the population of pro-inflammatory interstitial macrophages (IMs) and reducing the population of\n                    <jats:italic>Mtb<\/jats:italic>\n                    susceptible alveolar macrophages (AMs), dendritic cells (DCs), and monocytes (MO). Additionally, we deduce that PRK causes the host macrophages to change their metabolic pathway from fatty acid metabolism to glycolytic metabolism around the log phage of bacterial multiplication. Further, we report that PRK reduced tissue injury by downregulating the Ly6C-positive population of monocytes. Interestingly, PRK treatment improved tissue repair and inflammation resolution by increasing the populations of arginase 1 (Arg-1) and Ym1+Ym2 (chitinase 3-like 3) positive macrophages. In summary, our study found that PRK is useful not only for reducing the tubercular burden but also for promoting the healing of the diseased tissue.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1347045","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:31:34Z","timestamp":1714609894000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Antimycobacterial and healing effects of Pranlukast against MTB infection and pathogenesis in a preclinical mouse model of tuberculosis"],"prefix":"10.3389","volume":"15","author":[{"given":"Raju S.","family":"Rajmani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avadhesha","family":"Surolia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"B1","volume-title":"Global tuberculosis report","year":"2022"},{"key":"B2","volume-title":"WHO consolidated guidelines on tuberculosis. module 4: treatment-drug-resistant tuberculosis treatment 2022 Update","year":"2022"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.5.2007122","article-title":"The need for new drugs against tuberculosis. Obstacles, opportunities, and next steps","volume":"163","author":"O\u2019Brien","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"B4","article-title":"Differential proteomics approach to identify putative protective antigens of Mycobacterium tuberculosis presented during early stages of macrophage infection and their evaluation as DNA vaccines","volume":"53","author":"Sharma","year":"2015","journal-title":"Indian J Exp Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2016.01.014","article-title":"Extensively drug-resistant tuberculosis: principles of resistance, diagnosis, and management","volume":"91","author":"Wilson","year":"2016","journal-title":"Mayo Clin Proc"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1215294","article-title":"Editorial: drug-resistant mycobacterium tuberculosis","volume":"13","author":"Boshoff","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.14-3-279","article-title":"Multidrug-resistant and extensively drug-resistant tuberculosis: a review of current concepts and future challenges","volume":"14","author":"G\u00fcnther","year":"2014","journal-title":"Clin Med (Lond)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1126\/scitranslmed.aaw6635","article-title":"Targeting redox heterogeneity to counteract drug tolerance in replicating Mycobacterium tuberculosis","volume":"11","author":"Mishra","year":"2019","journal-title":"Sci Transl Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/nrd4001","article-title":"Advances in the development of new tuberculosis drugs and treatment regimens","volume":"12","author":"Zumla","year":"2013","journal-title":"Nat Rev Drug Discovery"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-1-201","article-title":"Attacking pathogens through their hosts","volume":"7","author":"Kellam","year":"2006","journal-title":"Genome Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1128\/mSphere.00043-15","article-title":"Targeting drug-sensitive and -resistant strains of mycobacterium tuberculosis by inhibition of src family kinases lowers disease burden and pathology","volume":"1","author":"Chandra","year":"2016","journal-title":"mSphere"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1054\/tuld.1998.0200","article-title":"The capsule of Mycobacterium tuberculosis and its implications for pathogenicity","volume":"79","author":"Daff\u00e9","year":"1999","journal-title":"Tuber Lung Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.14","article-title":"Macrophages and control of granulomatous inflammation in tuberculosis","volume":"4","author":"Flynn","year":"2011","journal-title":"Mucosal Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/imr.12223","article-title":"Macrophage heterogeneity in tissues: phenotypic diversity and functions","volume":"262","author":"Gordon","year":"2014","journal-title":"Immunol Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1165\/rcmb.2016-0361OC","article-title":"Three unique interstitial macrophages in the murine lung at steady state","volume":"57","author":"Gibbings","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.016","article-title":"Exposure to bacterial cpG DNA protects from airway allergic inflammation by expanding regulatory lung interstitial macrophages","volume":"46","author":"Sabatel","year":"2017","journal-title":"Immunity"},{"key":"B18","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.chom.2018.08.001","article-title":"Alveolar macrophages provide an early mycobacterium tuberculosis niche and initiate dissemination","volume":"24","author":"Cohen","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20172020","article-title":"Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny","volume":"215","author":"Huang","year":"2018","journal-title":"J Exp Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.celrep.2019.12.033","article-title":"Dual RNA-seq of mtb-infected macrophages in vivo reveals ontologically distinct host-pathogen interactions","volume":"30","author":"Pisu","year":"2020","journal-title":"Cell Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131199","article-title":"Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF","volume":"210","author":"Guilliams","year":"2013","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4172\/2161-105X.1000e133","article-title":"M. tuberculosis and macrophages: co-existence and co-evolution","volume":"4","author":"Liu","year":"2016","journal-title":"J Pulm Respir Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e1000839","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":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.012","article-title":"Genome-wide analysis of the host intracellular network that regulates survival of mycobacterium tuberculosis","volume":"140","author":"Kumar","year":"2010","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/thx.52.6.523","article-title":"Pranlukast, a novel leukotriene receptor antagonist: results of the first European, placebo controlled, multicentre clinical study in asthma","volume":"52","author":"Barnes","year":"1997","journal-title":"Thorax"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708038","article-title":"An allosteric inhibitor of Mycobacterium tuberculosis ArgJ: Implications to a novel combinatorial therapy","volume":"10","author":"Mishra","year":"2018","journal-title":"EMBO Mol Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.797563","article-title":"Protein kinase G confers survival advantage to Mycobacterium tuberculosis during latency-like conditions","volume":"292","author":"Khan","year":"2017","journal-title":"J Biol Chem"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0041-3879(60)80019-0","article-title":"A comparison of the virulence in Guinea-pigs of South Indian and British tubercle bacilli","volume":"41","author":"Mitchison","year":"1960","journal-title":"Tubercle"},{"key":"B29","first-page":"667","article-title":"Physiological, hematological and clinical chemistry parameters, including conversion factors","volume-title":"CRC Handbook of laboratory animal science","author":"Ostergaard","year":"2011"},{"key":"B30","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1126\/sciimmunol.aat0207","article-title":"Emergence of immunoregulatory Ym1 + Ly6C hi monocytes during recovery phase of tissue injury","volume":"3","author":"Ikeda","year":"2018","journal-title":"Sci Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.4.2509","article-title":"Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo","volume":"179","author":"Wolf","year":"2007","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12217","article-title":"Beyond macrophages: the diversity of mononuclear cells in tuberculosis","volume":"262","author":"Srivastava","year":"2014","journal-title":"Immunol Rev"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008621","article-title":"CD11cHi monocyte-derived macrophages are a major cellular compartment infected by Mycobacterium tuberculosis","volume":"16","author":"Lee","year":"2020","journal-title":"PLoS Pathog"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142322","article-title":"TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer\u2019s disease mouse models","volume":"212","author":"Jay","year":"2015","journal-title":"J Exp Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in tissue repair, regeneration, and fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070885","article-title":"The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions","volume":"204","author":"Nahrendorf","year":"2007","journal-title":"J Exp Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1189\/jlb.0409236","article-title":"The phenotype of murine wound macrophages","volume":"87","author":"Daley","year":"2010","journal-title":"J Leukoc Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/path.2277","article-title":"Cellular and molecular mechanisms of fibrosis","volume":"214","author":"Wynn","year":"2008","journal-title":"J Pathol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.08.011","article-title":"Uptake of neutrophil-derived Ym1 protein distinguishes wound macrophages in the absence of interleukin-4 signaling in murine wound healing","volume":"184","author":"Goren","year":"2014","journal-title":"Am J Pathol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1189\/jlb.71.4.597","article-title":"Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages","volume":"71","author":"Raes","year":"2002","journal-title":"J Leukoc Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.6561","article-title":"Arginase-1 and Ym1 are markers for murine, but not human, alternatively activated myeloid cells","volume":"174","author":"Raes","year":"2005","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205873200","article-title":"TH2 cytokines and allergic challenge induce Ym1 expression in macrophages by a STAT6-dependent mechanism","volume":"277","author":"Welch","year":"2002","journal-title":"J Biol Chem"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12092","article-title":"Infection of macrophages with Mycobacterium tuberculosis induces global modifications to phagosomal function","volume":"15","author":"Podinovskaia","year":"2013","journal-title":"Cell Microbiol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1086\/426395","article-title":"Macrophages play a dual role during pulmonary tuberculosis in mice","volume":"191","author":"Leemans","year":"2005","journal-title":"J Infect Dis"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40817","article-title":"Intranasal Poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte\/macrophage population","volume":"120","author":"Antonelli","year":"2010","journal-title":"J Clin Invest"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903356","article-title":"Differential roles of macrophages in diverse phases of skin repair","volume":"184","author":"Lucas","year":"2010","journal-title":"J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1347045\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:31:38Z","timestamp":1714609898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1347045\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,2]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2024.1347045"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1347045","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,2]]},"article-number":"1347045"}}