{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T11:30:42Z","timestamp":1791718242366,"version":"4.3.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immunonutrition as a therapeutic approach is rapidly gaining interest in the fight against infection. Targeting l-arginine metabolism is intriguing, considering this amino acid is the substrate for antimicrobial NO production by macrophages. The importance of l-arginine during infection is supported by the finding that inhibiting its synthesis from its precursor l-citrulline blunts host defense. During the first few weeks following pulmonary mycobacterial infection, we found a drastic increase in l-citrulline in the lung, even though serum concentrations were unaltered. This correlated with increased gene expression of the l-citrulline\u2013generating (i.e., iNOS) and l-citrulline\u2013using (i.e., Ass1) enzymes in key myeloid populations. Eliminating l-arginine synthesis from l-citrulline in myeloid cells via conditional deletion of either Ass1 or Asl resulted in increased Mycobacterium bovis bacillus Calmette-Gu\u00e9rin and Mycobacterium tuberculosis H37Rv burden in the lungs compared with controls. Our data illustrate the necessity of l-citrulline metabolism for myeloid defense against mycobacterial infection and highlight the potential for host-directed therapy against mycobacterial disease targeting this nutrient and\/or its metabolic pathway.<\/jats:p>","DOI":"10.4049\/jimmunol.1801569","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T23:00:40Z","timestamp":1549062040000},"page":"1747-1754","source":"Crossref","is-referenced-by-count":39,"title":["<scp>l<\/scp>-Arginine Synthesis from <scp>l<\/scp>-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3907-6072","authenticated-orcid":false,"given":"Shannon M","family":"Lange","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229"},{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"},{"name":"Immunology Graduate Program, College of Medicine, University of Cincinnati, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie C","family":"McKell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229"},{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"},{"name":"Immunology Graduate Program, College of Medicine, University of Cincinnati, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229"},{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-5665","authenticated-orcid":false,"given":"Junfang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Core, Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3190-9498","authenticated-orcid":false,"given":"Rebecca R","family":"Crowther","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229"},{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"},{"name":"Immunology Graduate Program, College of Medicine, University of Cincinnati, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229"},{"name":"Medical Scientist Training Program, College of Medicine, University of Cincinnati , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa C","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229"},{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"},{"name":"Molecular, Cellular, and Biochemical Pharmacology Graduate Program, College of Medicine, University of Cincinnati , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L","family":"Bricker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229"},{"name":"Division of Infectious Diseases, Cincinnati Children\u2019s Hospital Medical 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