{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:18:49Z","timestamp":1789852729224,"version":"4.0.1"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RO1AI083364"],"award-info":[{"award-number":["RO1AI083364"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Our previous study demonstrated that neutrophils play an important role in host defense against<jats:named-content content-type=\"genus-species\">Coxiella burnetii<\/jats:named-content>infection in mice. In this study, avirulent strain<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>Nine Mile phase II (NMII) was used to examine if<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>can modulate mouse bone marrow-derived neutrophil apoptosis. The results indicated that NMII can inhibit neutrophil apoptosis. Western blotting demonstrated that caspase-3 cleavage was decreased in NMII-infected neutrophils, while phosphorylated mitogen-activated protein kinase (MAPK) p38 and extracellular signal-regulated kinase 1 (Erk1) were increased. Additionally, p38, Erk1\/2, phosphoinositide 3-kinase (PI3K), or NF-\u03baB inhibitors reduced the ability of NMII to inhibit neutrophil apoptosis. These results suggest that NMII-mediated inhibition of neutrophil apoptosis depends on its ability to activate neutrophil MAPK pathways. Antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) was significantly increased in NMII-infected neutrophils, and an Mcl-1 inhibitor significantly reduced the ability of NMII to inhibit neutrophil apoptosis. Mcl-1 protein stability was enhanced by phosphorylation at Thr-163 by Erk, and the protein levels were regulated by p38, Erk, PI3K, and NF-\u03baB. Furthermore, the observation that a type IV secretion system (T4SS)-deficient<jats:italic>dotA<\/jats:italic>mutant showed a significantly reduced ability to inhibit neutrophil apoptosis compared to wild-type (WT) NMII suggests that T4SS-secreted factors may be involved in NMII-induced inhibition of neutrophil apoptosis. Collectively, these results demonstrate that NMII inhibits neutrophil apoptosis through inhibition of caspase-3 cleavage and activation of MAPK survival pathways with subsequent expression and stabilization of antiapoptotic protein Mcl-1, a process that may partially require the T4SS.<\/jats:p>","DOI":"10.1128\/iai.00504-17","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T12:00:46Z","timestamp":1515412846000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Coxiella burnetii Inhibits Neutrophil Apoptosis by Exploiting Survival Pathways and Antiapoptotic Protein Mcl-1"],"prefix":"10.1128","volume":"86","author":[{"given":"Rama","family":"Cherla","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri\u2014Columbia, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri\u2014Columbia, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Ledbetter","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri\u2014Columbia, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri\u2014Columbia, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)70052-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2011.00876.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.2.167"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.48.2.359-365.1985"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2011.0670"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.5.1144-1150.1987"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3024"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01487042"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.538"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3355"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00042-15"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113970"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2007.11.010"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.4049\/jimmunol.156.10.3986","article-title":"Neutrophils undergo apoptosis following ingestion of Escherichia coli","volume":"156","author":"Watson RW","year":"1996","unstructured":"Watson RW, Redmond HP, Wang JH, Condron C, Bouchier-Hayes D. 1996. Neutrophils undergo apoptosis following ingestion of Escherichia coli. J Immunol 156:3986\u20133992.","journal-title":"J Immunol"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1833375100"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:APPT.0000031448.64969.fa"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.4.1995-2001.2003"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.2.898"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1768"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00594-07"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00863-07"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030841"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00694-16"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00973-13"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000049506"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri957"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21078"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2003.00038.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2010.169"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-013771"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12432"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3049"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1139280"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12066"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004380107"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1785"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00550.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/7.5.507"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00741.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.8.2012.2012"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.8.3181.3181"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.54.4.283"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.3.1125-1133.2000"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00004-0"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.8.4286"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.12.8209-8218.2005"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2006.06.002"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00720.x"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02355.x"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020045"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01124-08"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2006.11.016"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.11.7039-7045.2001"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.8.4646"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00785.x"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060766"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2004.00440.x"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020115"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-008-8049-6"},{"key":"e_1_3_3_61_2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1189\/jlb.70.5.783","article-title":"BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis","volume":"70","author":"Moulding DA","year":"2001","unstructured":"Moulding DA, Akgul C, Derouet M, White MR, Edwards SW. 2001. BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis. J Leukoc Biol 70:783\u2013792.","journal-title":"J Leukoc Biol"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3516"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2876518"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207692"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.02.009"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093837"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01729-14"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1995.tb03254.x"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02826-10"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1401s83"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00504-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00504-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T13:22:23Z","timestamp":1693401743000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00504-17"}},"subtitle":[],"editor":[{"given":"Craig R.","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":69,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1128\/IAI.00504-17"],"URL":"https:\/\/doi.org\/10.1128\/iai.00504-17","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"2017-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00504-17"}}