{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:28:51Z","timestamp":1790634531037,"version":"4.1.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T00:00:00Z","timestamp":1496620800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T00:00:00Z","timestamp":1496620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pyrin domain-only proteins (POPs) are recently evolved, primate-specific proteins demonstrated<jats:italic>in vitro<\/jats:italic>as negative regulators of inflammatory responses. However, their<jats:italic>in vivo<\/jats:italic>function is not understood. Of the four known POPs, only POP2 is reported to regulate NF-\u03baB-dependent transcription and multiple inflammasomes. Here we use a transgenic mouse-expressing<jats:italic>POP2<\/jats:italic>controlled by its endogenous human promotor to study the immunological functions of POP2. Despite having significantly reduced inflammatory cytokine responses to LPS and bacterial infection, POP2 transgenic mice are more resistant to bacterial infection than wild-type mice. In a pulmonary tularaemia model, POP2 enhances IFN-\u03b3 production, modulates neutrophil numbers, improves macrophage functions, increases bacterial control and diminishes lung pathology. Thus, unlike other POPs thought to diminish innate protection, POP2 reduces detrimental inflammation while preserving and enhancing protective immunity. Our findings suggest that POP2 acts as a high-order regulator balancing cellular function and inflammation with broad implications for inflammation-associated diseases and therapeutic intervention.<\/jats:p>","DOI":"10.1038\/ncomms15564","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T12:19:22Z","timestamp":1496665162000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pyrin-only protein 2 limits inflammation but improves protection against bacteria"],"prefix":"10.1038","volume":"8","author":[{"given":"Sivakumar","family":"Periasamy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maninjay K.","family":"Atianand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongnga","family":"T. Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Earley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen B.","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Haller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0350-1877","authenticated-orcid":false,"given":"Jonathan A.","family":"Harton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,5]]},"reference":[{"key":"BFncomms15564_CR1","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1146\/annurev.immunol.21.120601.141126","volume":"21","author":"K Takeda","year":"2003","unstructured":"Takeda, K., Kaisho, T. & Akira, S. Toll-like receptors. Annu. Rev. Immunol. 21, 335\u2013376 (2003).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms15564_CR2","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","volume":"10","author":"F Martinon","year":"2002","unstructured":"Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 10, 417\u2013426 (2002).","journal-title":"Mol. Cell"},{"key":"BFncomms15564_CR3","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1146\/annurev.immunol.021908.132715","volume":"27","author":"F Martinon","year":"2009","unstructured":"Martinon, F., Mayor, A. & Tschopp, J. The inflammasomes: guardians of the body. Annu. Rev. Immunol. 27, 229\u2013265 (2009).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms15564_CR4","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1146\/annurev-immunol-031210-101405","volume":"29","author":"BK Davis","year":"2011","unstructured":"Davis, B. K., Wen, H. & Ting, J. P. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu. Rev. Immunol. 29, 707\u2013735 (2011).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms15564_CR5","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1042\/bj20030304","volume":"373","author":"C Stehlik","year":"2003","unstructured":"Stehlik, C. et al. The PAAD\/PYRIN-only protein POP1\/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation. Biochem. J. 373, 101\u2013113 (2003).","journal-title":"Biochem. J."},{"key":"BFncomms15564_CR6","doi-asserted-by":"publisher","first-page":"7993","DOI":"10.4049\/jimmunol.179.12.7993","volume":"179","author":"C Stehlik","year":"2007","unstructured":"Stehlik, C. & Dorfleutner, A. COPs and POPs: modulators of inflammasome activity. J. Immunol. 179, 7993\u20137998 (2007).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR7","doi-asserted-by":"publisher","first-page":"3837","DOI":"10.4049\/jimmunol.178.6.3837","volume":"178","author":"F Bedoya","year":"2007","unstructured":"Bedoya, F., Sandler, L. L. & Harton, J. A. Pyrin-only protein 2 modulates NF-kappaB and disrupts ASC:CLR interactions. J. Immunol. 178, 3837\u20133845 (2007).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR8","doi-asserted-by":"publisher","first-page":"e1000635","DOI":"10.1371\/journal.ppat.1000635","volume":"5","author":"MM Rahman","year":"2009","unstructured":"Rahman, M. M. et al. Co-regulation of NF-kappaB and inflammasome-mediated inflammatory responses by myxoma virus pyrin domain-containing protein M013. PLoS Pathog. 5, e1000635 (2009).","journal-title":"PLoS Pathog."},{"key":"BFncomms15564_CR9","doi-asserted-by":"publisher","first-page":"40536","DOI":"10.1074\/jbc.M111.274290","volume":"286","author":"MK Atianand","year":"2011","unstructured":"Atianand, M. K. & Harton, J. A. Uncoupling of Pyrin-only protein 2 (POP2) mediated dual-regulation of NF-\u03baB and the inflammasome. J. Biol. Chem. 286, 40536\u201340547 (2011).","journal-title":"J. Biol. Chem."},{"key":"BFncomms15564_CR10","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/1471-2148-11-56","volume":"11","author":"M Atianand","year":"2011","unstructured":"Atianand, M., Fuchs, T. & Harton, J. A. Recent evolution of the NF-kappaB and inflammasome regulating protein POP2 in primates. BMC Evolut. Biol. 11, 56 (2011).","journal-title":"BMC Evolut. Biol."},{"key":"BFncomms15564_CR11","first-page":"275","volume":"4","author":"HT Le","year":"2013","unstructured":"Le, H. T. & Harton, J. A. Pyrin- and CARD-only roteins as regulators of NLR functions. Front. Immunol. 4, 275 (2013).","journal-title":"Front. Immunol."},{"key":"BFncomms15564_CR12","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/ni.2829","volume":"15","author":"S Khare","year":"2014","unstructured":"Khare, S. et al. The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. Nat. Immunol. 15, 343\u2013353 (2014).","journal-title":"Nat. Immunol."},{"key":"BFncomms15564_CR13","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/gene.2014.30","volume":"15","author":"KA Porter","year":"2014","unstructured":"Porter, K. A. et al. The CLRX.1\/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NF-\u03baB, pyrin-only protein 4. Genes Immun. 15, 392\u2013403 (2014).","journal-title":"Genes Immun."},{"key":"BFncomms15564_CR14","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.immuni.2015.07.018","volume":"43","author":"L de Almeida","year":"2015","unstructured":"de Almeida, L. et al. The PYRIN domain-only Protein POP1 inhibits inflammasome assembly and ameliorates inflammatory disease. Immunity 43, 264\u2013276 (2015).","journal-title":"Immunity"},{"key":"BFncomms15564_CR15","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/0092-8674(81)90019-2","volume":"66","author":"DB Dynlacht","year":"1991","unstructured":"Dynlacht, D. B., Hoey, T. & Tjian, R. Isolation of coactivators associated with the TATA-binding protein that mediates transcriptional activation. Cell 66, 563\u2013576 (1991).","journal-title":"Cell"},{"key":"BFncomms15564_CR16","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1099\/00221287-19-3-497","volume":"19","author":"D Kerridge","year":"1958","unstructured":"Kerridge, D. The effect of actidione and other antifungal agents on nucleic acid and protein synthesis in Saccharomyces carlsbergensis. J. Gen. Microbiol. 19, 497\u2013506 (1958).","journal-title":"J. Gen. Microbiol."},{"key":"BFncomms15564_CR17","doi-asserted-by":"publisher","first-page":"5328","DOI":"10.1073\/pnas.82.16.5328","volume":"82","author":"HM Sobell","year":"1985","unstructured":"Sobell, H. M. Actinomycin and DNA transcription. PNAS 82, 5328\u20135331 (1985).","journal-title":"PNAS"},{"key":"BFncomms15564_CR18","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1073\/pnas.83.6.1670","volume":"83","author":"D Caput","year":"1986","unstructured":"Caput, D. et al. Identification of a common nucleotide sequence in the 3\u2032-untranslated region of mRNA molecules specifying inflammatory mediators. PNAS 83, 1670\u20131674 (1986).","journal-title":"PNAS"},{"key":"BFncomms15564_CR19","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/0092-8674(86)90341-7","volume":"46","author":"G Shaw","year":"1986","unstructured":"Shaw, G. & Kamen, R. A conserved AU sequence from the 3\u2032 untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46, 659\u2013667 (1986).","journal-title":"Cell"},{"key":"BFncomms15564_CR20","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s11262-007-0141-9","volume":"35","author":"A Dorfleutner","year":"2007","unstructured":"Dorfleutner, A. et al. A Shope Fibroma virus PYRIN-only protein modulates the host immune response. Virus Genes 35, 685\u2013694 (2007).","journal-title":"Virus Genes"},{"key":"BFncomms15564_CR21","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1196\/annals.1409.006","volume":"1105","author":"JS Gunn","year":"2007","unstructured":"Gunn, J. S. & Ernst, R. K. The structure and function of Francisella lipopolysaccharide. Ann. N. Y. Acad. Sci. 1105, 202\u2013218 (2007).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"BFncomms15564_CR22","doi-asserted-by":"publisher","first-page":"6730","DOI":"10.1128\/IAI.00934-06","volume":"74","author":"AM Hajjar","year":"2006","unstructured":"Hajjar, A. M. et al. Lack of in vitro and in vivo recognition of Francisella tularensis subspecies lipopolysaccharide by Toll-like receptors. Infect. Immun. 74, 6730\u20136738 (2006).","journal-title":"Infect. Immun."},{"key":"BFncomms15564_CR23","doi-asserted-by":"publisher","first-page":"3657","DOI":"10.1128\/IAI.02030-05","volume":"74","author":"M Malik","year":"2006","unstructured":"Malik, M. et al. Toll-like receptor 2 is required for control of pulmonary infection with Francisella tularensis. Infect. Immun. 74, 3657\u20133662 (2006).","journal-title":"Infect. Immun."},{"key":"BFncomms15564_CR24","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/ni.1859","volume":"11","author":"T Fernandes-Alnemri","year":"2010","unstructured":"Fernandes-Alnemri, T. et al. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat. Immunol. 11, 385\u2013393 (2010).","journal-title":"Nat. Immunol."},{"key":"BFncomms15564_CR25","doi-asserted-by":"publisher","first-page":"9771","DOI":"10.1073\/pnas.1003738107","volume":"107","author":"JW Jones","year":"2010","unstructured":"Jones, J. W. et al. Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. PNAS 107, 9771\u20139776 (2010).","journal-title":"PNAS"},{"key":"BFncomms15564_CR26","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1002\/eji.201040425","volume":"40","author":"S Kim","year":"2010","unstructured":"Kim, S. et al. Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. Eur. J. Immunol. 40, 1545\u20131551 (2010).","journal-title":"Eur. J. Immunol."},{"key":"BFncomms15564_CR27","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/nature10510","volume":"477","author":"Y Zhao","year":"2011","unstructured":"Zhao, Y. et al. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature 477, 596\u2013600 (2011).","journal-title":"Nature"},{"key":"BFncomms15564_CR28","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/nri2711","volume":"10","author":"M Saraiva","year":"2010","unstructured":"Saraiva, M. & O\u2019Garra, A. The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 10, 170\u2013181 (2010).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms15564_CR29","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1111\/j.1462-5822.2008.01189.x","volume":"10","author":"LO Moreira","year":"2008","unstructured":"Moreira, L. O. et al. The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls. Cell Microbiol. 10, 2067\u20132077 (2008).","journal-title":"Cell Microbiol."},{"key":"BFncomms15564_CR30","doi-asserted-by":"crossref","first-page":"5936","DOI":"10.4049\/jimmunol.160.12.5936","volume":"160","author":"M Aste-Amezaga","year":"1998","unstructured":"Aste-Amezaga, M., Ma, X., Sartori, A. & Trinchieri, G. Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. J. Immunol. 160, 5936\u20135944 (1998).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR31","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1126\/science.3895437","volume":"229","author":"B Beutler","year":"1985","unstructured":"Beutler, B., Milsark, I. W. & Cerami, A. C. Passive immunization against cachectin\/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229, 869\u2013871 (1985).","journal-title":"Science"},{"key":"BFncomms15564_CR32","doi-asserted-by":"publisher","first-page":"8093","DOI":"10.1073\/pnas.94.15.8093","volume":"94","author":"MW Marino","year":"1997","unstructured":"Marino, M. W. et al. Characterization of tumor necrosis factor-deficient mice. PNAS 94, 8093\u20138098 (1997).","journal-title":"PNAS"},{"key":"BFncomms15564_CR33","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1002\/jlb.59.4.489","volume":"59","author":"G Fantuzzi","year":"1996","unstructured":"Fantuzzi, G. & Dinarello, C. A. The inflammatory response in interleukin-1 beta-deficient mice: comparison with other cytokine-related knock-out mice. J. Leukoc. Biol. 59, 489\u2013493 (1996).","journal-title":"J. Leukoc. Biol."},{"key":"BFncomms15564_CR34","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/nature04515","volume":"440","author":"S Mariathasan","year":"2006","unstructured":"Mariathasan, S. et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228\u2013232 (2006).","journal-title":"Nature"},{"key":"BFncomms15564_CR35","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nri3399","volume":"13","author":"E Kolaczkowska","year":"2013","unstructured":"Kolaczkowska, E. & Kubes, P. Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13, 159\u2013175 (2013).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms15564_CR36","doi-asserted-by":"publisher","first-page":"e1005517","DOI":"10.1371\/journal.ppat.1005517","volume":"12","author":"S Periasamy","year":"2016","unstructured":"Periasamy, S. et al. An immature myeloid\/myeloid-suppressor cell response associated with necrotizing inflammation mediates lethal pulmonary tularaemia. PLoS Pathog. 12, e1005517 (2016).","journal-title":"PLoS Pathog."},{"key":"BFncomms15564_CR37","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1086\/589620","volume":"198","author":"SC Cowley","year":"2008","unstructured":"Cowley, S. C., Goldberg, M. F., Ho, J. A. & Elkins, K. L. The membrane form of tumor necrosis factor is sufficient to mediate partial innate immunity to Francisella tularensis live vaccine strain. J. Infect. Dis. 198, 284\u2013292 (2008).","journal-title":"J. Infect. Dis."},{"key":"BFncomms15564_CR38","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1128\/IAI.01249-12","volume":"81","author":"SL Kurtz","year":"2013","unstructured":"Kurtz, S. L. et al. Interleukin-6 is essential for primary resistance to Francisella tularensis live vaccine strain infection. Infect. Immun. 81, 585\u2013597 (2013).","journal-title":"Infect. Immun."},{"key":"BFncomms15564_CR39","doi-asserted-by":"publisher","first-page":"e1004706","DOI":"10.1371\/journal.ppat.1004706","volume":"11","author":"L del Barrio","year":"2015","unstructured":"del Barrio, L. et al. Production of anti-LPS IgM by B1a B cells depends on IL-1\u03b2 and is protective against lung infection with Francisella tularensis LVS. PLoS Pathog. 11, e1004706 (2015).","journal-title":"PLoS Pathog."},{"key":"BFncomms15564_CR40","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1189\/jlb.0603252","volume":"75","author":"K Schroder","year":"2004","unstructured":"Schroder, K., Hertzog, P. J., Ravasi, T. & Hume, D. A. Interferon-gamma: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75, 163\u2013189 (2004).","journal-title":"J. Leukoc. Biol."},{"key":"BFncomms15564_CR41","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.micinf.2009.09.012","volume":"12","author":"KL Elkins","year":"2010","unstructured":"Elkins, K. L. et al. Survival of secondary lethal systemic Francisella tularensis LVS challenge depends largely on interferon gamma. Microbes Infect. 12, 28\u201336 (2010).","journal-title":"Microbes Infect."},{"key":"BFncomms15564_CR42","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1099\/mic.0.031716-0","volume":"156","author":"JA Edwards","year":"2010","unstructured":"Edwards, J. A., Rockx-Brouwer, D., Nair, V. & Celli, J. Restricted cytosolic growth of Francisella tularensis subsp. tularensis by IFN-gamma activation of macrophages. Microbiology. 156, 327\u2013339 (2010).","journal-title":"Microbiology."},{"key":"BFncomms15564_CR43","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.micpath.2004.02.003","volume":"36","author":"W Chen","year":"2004","unstructured":"Chen, W., KuoLee, R., Shen, H. & Conlan, J. W. Susceptibility of immunodeficient mice to aerosol and systemic infection with virulent strains of Francisella tularensis. Microb. Pathog. 36, 311\u2013318 (2004).","journal-title":"Microb. Pathog."},{"key":"BFncomms15564_CR44","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1128\/IAI.73.4.2306-2311.2005","volume":"73","author":"NS Duckett","year":"2005","unstructured":"Duckett, N. S., Olmos, S., Durrant, D. M. & Metzger, D. W. Intranasal interleukin-12 treatment for protection against respiratory infection with the Francisella tularensis live vaccine strain. Infect. Immun. 73, 2306\u20132311 (2005).","journal-title":"Infect. Immun."},{"key":"BFncomms15564_CR45","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/S1471-4906(01)02005-1","volume":"22","author":"DM Frucht","year":"2001","unstructured":"Frucht, D. M. et al. IFN-gamma production by antigen-presenting cells: mechanisms emerge. Trends Immunol. 22, 556\u2013560 (2001).","journal-title":"Trends Immunol."},{"key":"BFncomms15564_CR46","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1080\/07391102.2010.10508574","volume":"27","author":"P Putta","year":"2010","unstructured":"Putta, P. & Mitra, C. K. Conserved short sequences in promoter regions of human genome. J. Biomol. Struct. Dyn. 27, 599\u2013610 (2010).","journal-title":"J. Biomol. Struct. Dyn."},{"key":"BFncomms15564_CR47","doi-asserted-by":"publisher","first-page":"51897","DOI":"10.1074\/jbc.M406741200","volume":"279","author":"JM Bruey","year":"2004","unstructured":"Bruey, J. M. et al. PAN1\/NALP2\/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages. J. Biol. Chem. 279, 51897\u201307 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFncomms15564_CR48","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.ceb.2008.03.003","volume":"20","author":"T Juven-Gershon","year":"2008","unstructured":"Juven-Gershon, T., Hsu, J. Y., Theisen, J. W. & Kadonaga, J. T. The RNA polymerase II core promoter-the gateway to transcription. Curr. Opin. Cell Biol. 20, 253\u2013259 (2008).","journal-title":"Curr. Opin. Cell Biol."},{"key":"BFncomms15564_CR49","doi-asserted-by":"publisher","first-page":"7219","DOI":"10.1074\/jbc.270.13.7219","volume":"270","author":"ML Schmitz","year":"1995","unstructured":"Schmitz, M. L. et al. Interaction of the COOH-terminal transactivation domain of p65 NF-kappa B with TATA-binding protein, transcription factor IIB, and coactivators. J. Biol. Chem. 270, 7219\u20137226 (1995).","journal-title":"J. Biol. Chem."},{"key":"BFncomms15564_CR50","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/ni.1699","volume":"10","author":"S Hao","year":"2009","unstructured":"Hao, S. & Baltimore, D. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat. Immunol. 10, 281\u2013288 (2009).","journal-title":"Nat. Immunol."},{"key":"BFncomms15564_CR51","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/1471-2164-13-182","volume":"13","author":"M Iwanaszko","year":"2012","unstructured":"Iwanaszko, M., Brasier, A. R. & Kimmel, M. The dependence of expression of NF-\u03baB-dependent genes: statistics and evolutionary conservation of control sequences in the promoter and in the 3\u2032 UTR. BMC Genomics 13, 82 (2012).","journal-title":"BMC Genomics"},{"key":"BFncomms15564_CR52","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/S0968-0004(00)89102-1","volume":"20","author":"CY Chen","year":"1995","unstructured":"Chen, C. Y. & Shyu, A. B. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem. Sci. 20, 465\u2013470 (1995).","journal-title":"Trends Biochem. Sci."},{"key":"BFncomms15564_CR53","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1093\/jb\/mvs010","volume":"151","author":"A Barker","year":"2012","unstructured":"Barker, A. et al. Sequence requirements for RNA binding by HuR and AUF1. J. Biochem. 151, 423\u2013437 (2012).","journal-title":"J. Biochem."},{"key":"BFncomms15564_CR54","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.bcmd.2007.06.010","volume":"39","author":"AD Friedman","year":"2007","unstructured":"Friedman, A. D. C\/EBPalpha induces PU.1 and interacts with AP-1 and NF-kappaB to regulate myeloid development. Blood Cells Mol. Dis. 39, 340\u2013343 (2007).","journal-title":"Blood Cells Mol. Dis."},{"key":"BFncomms15564_CR55","doi-asserted-by":"publisher","first-page":"5757","DOI":"10.4049\/jimmunol.0803861","volume":"182","author":"D Wang","year":"2009","unstructured":"Wang, D., Paz-Priel, I. & Friedman, A. D. NF-kappa B p50 regulates C\/EBP alpha expression and inflammatory cytokine-induced neutrophil production. J. Immunol. 182, 5757\u20135762 (2009).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR56","doi-asserted-by":"publisher","first-page":"doi:10.1038\/nco","DOI":"10.1038\/ncomms15556","volume":"8,","author":"RA Ratsimandresy","year":"2017","unstructured":"Ratsimandresy, R. A. et al. The PYRIN domain-only protein POP2 inhibits inflammasome priming and activation. Nat. Commun. 8,, doi:10.1038\/ncomms15556 (2017).","journal-title":"Nat. Commun."},{"key":"BFncomms15564_CR57","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1128\/iai.62.7.2779-2783.1994","volume":"62","author":"A Sj\u00f6stedt","year":"1994","unstructured":"Sj\u00f6stedt, A., Conlan, J. W. & North, R. J. Neutrophils are critical for host defense against primary infection with the facultative intracellular bacterium Francisella tularensis in mice and participate in defense against reinfection. Infect. Immun. 62, 2779\u20132783 (1994).","journal-title":"Infect. Immun."},{"key":"BFncomms15564_CR58","doi-asserted-by":"publisher","first-page":"3195","DOI":"10.4049\/jimmunol.168.7.3195","volume":"168","author":"JH Dufour","year":"2002","unstructured":"Dufour, J. H. et al. IFN-\u03b3-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J. Immunol. 168, 3195\u20133204 (2002).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR59","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fimmu.2012.00276","volume":"3","author":"SC Yung","year":"2012","unstructured":"Yung, S. C. & Murphy, P. M. Antimicrobial chemokines. Front. Immunol. 3, 276 (2012).","journal-title":"Front. Immunol."},{"key":"BFncomms15564_CR60","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.immuni.2009.09.002","volume":"31","author":"X Hu","year":"2009","unstructured":"Hu, X. & Ivashkiv, L. B. Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases. Immunity 31, 539\u2013550 (2009).","journal-title":"Immunity"},{"key":"BFncomms15564_CR61","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1189\/jlb.0806486","volume":"81","author":"H Kelchtermans","year":"2007","unstructured":"Kelchtermans, H. et al. Protective role of IFN-gamma in collagen-induced arthritis conferred by inhibition of mycobacteria-induced granulocyte chemotactic protein-2 production. J. Leukoc. Biol. 81, 1044\u20131053 (2007).","journal-title":"J. Leukoc. Biol."},{"key":"BFncomms15564_CR62","doi-asserted-by":"publisher","first-page":"8057","DOI":"10.4049\/jimmunol.180.12.8057","volume":"180","author":"Y Hu","year":"2008","unstructured":"Hu, Y., Hu, X., Boumsell, L. & Ivashkiv, L. B. IFN-gamma and STAT1 arrest monocyte migration and modulate RAC\/CDC42 pathways. J. Immunol. 180, 8057\u20138065 (2008).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR63","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1182\/blood-2011-07-367706","volume":"119","author":"AM de Bruin","year":"2012","unstructured":"de Bruin, A. M. et al. IFN-gamma induces monopoiesis and inhibits neutrophil development during inflammation. Blood 119, 1543\u20131554 (2012).","journal-title":"Blood"},{"key":"BFncomms15564_CR64","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.4049\/jimmunol.1001893","volume":"186","author":"KC MacNamara","year":"2011","unstructured":"MacNamara, K. C. et al. Infection-induced myelopoiesis during intracellular bacterial infection is critically dependent upon IFN-\u03b3 signaling. J. Immunol. 186, 1032\u20131043 (2011).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR65","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nri3024","volume":"11","author":"A Mantovani","year":"2011","unstructured":"Mantovani, A., Cassatella, M. A., Costantini, C. & Jaillon, S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol. 11, 519\u2013531 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms15564_CR66","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.4049\/jimmunol.1500874","volume":"195","author":"EL Chiswick","year":"2015","unstructured":"Chiswick, E. L., Mella, J. R., Bernard, J. & Remick, D. G. Acute-phase deaths from murine polymicrobial sepsis are characterized by innate immune suppression rather than exhaustion. J. Immunol. 195, 3793\u20133802 (2015).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR67","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1365-2567.2004.01849.x","volume":"112","author":"TN Ellis","year":"2004","unstructured":"Ellis, T. N. & Beaman, B. L. Interferon-gamma activation of polymorphonuclear neutrophil function. Immunology 112, 2\u201312 (2004).","journal-title":"Immunology"},{"key":"BFncomms15564_CR68","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nrmicro2128","volume":"7","author":"RS Flannagan","year":"2009","unstructured":"Flannagan, R. S., Cosio, G. & Grinstein, S. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nat. Rev. Microbiol. 7, 355\u2013366 (2009).","journal-title":"Nat. Rev. Microbiol."},{"key":"BFncomms15564_CR69","doi-asserted-by":"publisher","first-page":"2666","DOI":"10.1002\/eji.200323292","volume":"33","author":"K Suzue","year":"2002","unstructured":"Suzue, K., Asai, T., Takeuchi, T. & Koyasu, S. In vivo role of IFN-gamma produced by antigen-presenting cells in early host defense against intracellular pathogens. Eur. J. Immunol. 33, 2666\u20132675 (2002).","journal-title":"Eur. J. Immunol."},{"key":"BFncomms15564_CR70","doi-asserted-by":"publisher","first-page":"15137","DOI":"10.1073\/pnas.261570598","volume":"98","author":"AA Lighvani","year":"2001","unstructured":"Lighvani, A. A. et al. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. PNAS 98, 15137\u201315142 (2001).","journal-title":"PNAS"},{"key":"BFncomms15564_CR71","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.4049\/jimmunol.161.4.1594","volume":"161","author":"MA Lokuta","year":"1998","unstructured":"Lokuta, M. A., McDowell, M. A. & Paulnock, D. M. Identification of an additional isoform of STAT5 expressed in immature macrophages. J. Immunol. 161, 1594\u20131597 (1998).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR72","doi-asserted-by":"publisher","first-page":"5660","DOI":"10.4049\/jimmunol.1300422","volume":"192","author":"F Herr","year":"2014","unstructured":"Herr, F. et al. IL-2 phosphorylates STAT5 to drive IFN-\u03b3 production and activation of human dendritic cells. J. Immunol. 192, 5660\u20135670 (2014).","journal-title":"J. Immunol."},{"key":"BFncomms15564_CR73","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/ni.3202","volume":"16","author":"M Bruchard","year":"2015","unstructured":"Bruchard, M. et al. The receptor NLRP3 is a transcriptional regulator of TH2 differentiation. Nat. Immunol. 16, 859\u2013870 (2015).","journal-title":"Nat. Immunol."},{"key":"BFncomms15564_CR74","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.cell.2011.04.022","volume":"145","author":"E Elinav","year":"2011","unstructured":"Elinav, E. et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145, 745\u2013757 (2011).","journal-title":"Cell"},{"key":"BFncomms15564_CR75","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1016\/j.cell.2015.10.048","volume":"163","author":"M Levy","year":"2015","unstructured":"Levy, M. et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163, 1428\u20131443 (2015).","journal-title":"Cell"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms15564.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms15564","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/ncomms15564","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms15564.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T22:30:26Z","timestamp":1692829826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms15564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,5]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,8,11]]}},"alternative-id":["BFncomms15564"],"URL":"https:\/\/doi.org\/10.1038\/ncomms15564","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,5]]},"assertion":[{"value":"8 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15564"}}