{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T23:19:38Z","timestamp":1785194378651,"version":"3.55.0"},"reference-count":77,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,9,12]],"date-time":"2013-09-12T00:00:00Z","timestamp":1378944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Opportunistic infections with non\u2010tuberculous mycobacteria such as <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>ycobacterium avium<\/jats:italic> are receiving renewed attention because of increased incidence and difficulties in treatment. As for other mycobacterial infections, a still poorly understood collaboration of different immune effector mechanisms is required to confer protective immunity. Here we have characterized the interplay of innate and adaptive immune effector mechanisms contributing to containment in a mouse infection model using virulent <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>.\u00a0avium<\/jats:italic> strain 104 in C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice. <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic>. <\/jats:styled-content><jats:italic>avium<\/jats:italic> caused chronic infection in mice, as shown by sustained organ bacterial load. In the liver, bacteria were contained in granuloma\u2010like structures that could be defined morphologically by expression of the antibacterial innate effector protein Lipocalin 2 in the adjoining hepatocytes and infiltrating neutrophils, possibly contributing to containment. Circulatory anti\u2010mycobacterial antibodies steadily increased throughout infection and were primarily of the <jats:styled-content style=\"fixed-case\">IgM<\/jats:styled-content> isotype. Highest levels of interferon\u2010\u03b3 were found in infected liver, spleen and serum of mice approximately 2\u00a0weeks post infection and coincided with a halt in organ bacterial growth. In contrast, expression of tumour necrosis factor was surprisingly low in spleen compared with liver. We did not detect interleukin\u201017 in infected organs or <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>.\u00a0avium<\/jats:italic>\u2010specific T helper 17 cells, suggesting a minor role for T helper 17 cells in this model. A transient and relative decrease in regulatory T cell numbers was seen in spleens. This detailed characterization of <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>.\u00a0avium<\/jats:italic> infection in C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice may provide a basis for future studies aimed at gaining better insight into mechanisms leading to containment of infections with non\u2010tuberculous mycobacteria.<\/jats:p>","DOI":"10.1111\/imm.12131","type":"journal-article","created":{"date-parts":[[2013,6,8]],"date-time":"2013-06-08T06:36:50Z","timestamp":1370673410000},"page":"232-243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Dynamics of immune effector mechanisms during infection with <i><scp>M<\/scp>ycobacterium avium<\/i> in <scp>C<\/scp>57<scp>BL<\/scp>\/6 mice"],"prefix":"10.1111","volume":"140","author":[{"given":"Markus","family":"Haug","sequence":"first","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Centre of Molecular Inflammation Research NTNU Trondheim"},{"name":"St Olav's Hospital Trondheim"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"Awuh","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Centre of Molecular Inflammation Research NTNU Trondheim"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Steigedal","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Centre of Molecular Inflammation Research NTNU Trondheim"},{"name":"St Olav's Hospital Trondheim"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June","family":"Frengen Kojen","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Centre of Molecular Inflammation Research NTNU Trondheim"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Marstad","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Centre of Molecular Inflammation Research NTNU Trondheim"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivar S.","family":"Nordrum","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Genetics St Olav's Hospital Trondheim"},{"name":"Department of Laboratory Medicine Children's and Women's Health NTNU Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8yvind","family":"Halaas","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Centre of Molecular Inflammation Research NTNU Trondheim"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trude H.","family":"Flo","sequence":"additional","affiliation":[{"name":"Department of Cancer Research and Molecular Medicine Centre of Molecular Inflammation Research NTNU Trondheim"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00130832-200112000-00003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-004-4001-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e328336ead6"},{"key":"e_1_2_8_5_1","first-page":"35","article-title":"Why does tumor necrosis factor targeted therapy reactivate tuberculosis?","volume":"74","author":"Ehlers S","year":"2005","journal-title":"J Rheumatol Suppl"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1510.090310"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/164.5.994"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199105093241906"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/324508"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/515091"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1404.060570"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201204-0682OC"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e3283511a64"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.8.1299"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.12.6879-6882.2000"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.11.6734"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2741\/A287"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:35:3:179"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1128\/iai.62.9.3962-3971.1994","article-title":"Role of \u03b3 interferon and tumor necrosis factor \u03b1 during T\u2010cell\u2010independent and \u2010dependent phases of Mycobacterium avium infection","volume":"62","author":"Appelberg R","year":"1994","journal-title":"Infect Immun"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5368.1432"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17552-1"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100066"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00545.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.13"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/650493"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8521"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4032"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.08.004"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2007.07.001"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200839148"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.03967.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-48-6-577"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2005.04.005"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838630"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2012.07.021"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.08.018"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2785"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.44.3.783-789.2006"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.18.6332-6334.2004"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2002.01121.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03104"},{"key":"e_1_2_8_42_1","doi-asserted-by":"crossref","first-page":"4822","DOI":"10.4049\/jimmunol.158.10.4822","article-title":"Defects in cell\u2010mediated immunity affect chronic, but not innate, resistance of mice to Mycobacterium avium infection","volume":"158","author":"Doherty TM","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09135"},{"key":"e_1_2_8_44_1","first-page":"88","article-title":"Splenomegaly in 2,505 patients at a large university medical center from 1913 to 1995. 1963 to 1995: 449 patients","volume":"169","author":"O'Reilly RA","year":"1998","journal-title":"West J Med"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184784"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010515"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510847103"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(00)00152-7"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.4161\/viru.1.5.12862"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100265"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.10"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1994.tb06127.x"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<127::AID-PATH398>3.0.CO;2-S"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01459.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1128\/IAI.67.7.3610-3618.1999","article-title":"Resistance of virulent Mycobacterium avium to \u03b3 interferon\u2010mediated antimicrobial activity suggests additional signals for induction of mycobacteriostasis","volume":"67","author":"Florido M","year":"1999","journal-title":"Infect Immun"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2011.04.004"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.9.3381-3387.1995"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.1999.4709"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.11.7222"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.05.009"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2005.12.004"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00384.x"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3571-3579.1999"},{"key":"e_1_2_8_64_1","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.4049\/jimmunol.140.9.3006","article-title":"Tumor necrosis factor, alone or in combination with IL\u20102, but not IFN\u2010\u03b3, is associated with macrophage killing of Mycobacterium avium complex","volume":"140","author":"Bermudez LE","year":"1988","journal-title":"J Immunol"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01878485"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90001-2"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00937.x"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801592"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1592"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201003-0334OC"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60177-4"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.10.3759-3764.1995"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1449"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2010.10.004"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1999.00563.x"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4662"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1416"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062105"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12131","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T16:53:08Z","timestamp":1696265588000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,12]]},"references-count":77,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1111\/imm.12131"],"URL":"https:\/\/doi.org\/10.1111\/imm.12131","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,12]]},"assertion":[{"value":"2013-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}