{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:48:44Z","timestamp":1793321324084,"version":"4.5.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071850, 82030095"],"award-info":[{"award-number":["82071850, 82030095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Fungal sepsis remains a major health threat with high mortality, where the adrenal gland stress response has been rarely reported. <jats:italic>Candida albicans<\/jats:italic> (<jats:italic>C.albicans<\/jats:italic>) is the most common opportunistic fungal pathogen of life-threatening disseminated candidiasis and fungal sepsis. In the present study, we performed single-cell RNA sequencing (scRNA-Seq) using the 10x Genomics platform to analyze the changes in murine adrenal transcriptome following systemic <jats:italic>C.albicans<\/jats:italic> infection. A total of 16 021 cells were categorized into 18 transcriptionally distinct clusters, representing adrenocortical cells, endothelial cells, various immune cells, mesenchymal cells, smooth muscle cells, adrenal capsule, chromaffin cells, neurons and glials. As the main cell component in the adrenal gland responsible for steroidogenesis, the adrenocortical cells dramatically diminished and were further grouped into 10 subclusters, which differently distributed in the infected and uninfected samples. Pseudo-time analysis revealed transitions of the adrenocortical cells from the initial normal states to active or dysfunctional states following systemic <jats:italic>C.albicans<\/jats:italic> infection <jats:italic>via<\/jats:italic> two trajectory paths. Endothelial cells in the highly vascularized organ of adrenal gland further proliferated following infection, with the upregulation of genes positively regulating angiogenesis and downregulation of protective genes of endothelial cells. Immune cells were also excessively infiltrated in adrenal glands of <jats:italic>C.albicans<\/jats:italic>-infected mice. Macrophages dominated the immune microenvironments in murine adrenal glands both before and after <jats:italic>C.albicans<\/jats:italic> infection, mediating the crosstalk among the steroid-producing cells, endothelial cells and immune cells within the adrenal gland. NLR family, pyrin domain containing 3 (NLRP3, encoded by <jats:italic>Nlrp3<\/jats:italic>) and complement receptor 3 (CR3, encoded by <jats:italic>Itgam<\/jats:italic>) were found to be significantly upregulated on the adrenal macrophages upon systemic <jats:italic>C.albicans<\/jats:italic> infection and might play critical roles in mediating the myeloid response. Meanwhile, the number and strength of the interactions between the infiltrating immune cells and adrenal resident cells were unveiled by cell-cell communication analysis to be dramatically increased after systemic <jats:italic>C.albicans<\/jats:italic> infection, indicating that the immune-adrenal crosstalk might contribute to the compromised functions of adrenal cells. Overall, our comprehensive picture of the murine adrenal gland microenvironment in systemic <jats:italic>C.albicans<\/jats:italic> infection provides deeper insights into the immune-adrenal cell communications during fungal sepsis.<\/jats:p>","DOI":"10.3389\/fimmu.2022.966814","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:05:31Z","timestamp":1667282731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Kai","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhe","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13255","article-title":"Candida albicans and candidalysin in inflammatory disorders and cancer","volume":"162","author":"Ho","year":"2021","journal-title":"Immunology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040057","article-title":"Global and multi-national prevalence of fungal diseases-estimate precision","volume":"3","author":"Bongomin","year":"2017","journal-title":"J fungi (Basel Switzerland)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4161\/viru.26187","article-title":"Invasive candidiasis as a cause of sepsis in the critically ill patient","volume":"5","author":"Delaloye","year":"2014","journal-title":"Virulence"},{"key":"B4","doi-asserted-by":"publisher","first-page":"6699","DOI":"10.1038\/s41467-021-27034-9","article-title":"Inflammasome-mediated gsdmd activation facilitates escape of candida albicans from macrophages","volume":"12","author":"Ding","year":"2021","journal-title":"Nat Commun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1744","article-title":"The adrenal gland microenvironment in health, disease and during regeneration","volume":"16","author":"Kanczkowski","year":"2017","journal-title":"Hormones (Athens Greece)"},{"key":"B6","first-page":"57","article-title":"Adrenal gland disorders","volume":"81","author":"Berry","year":"2009","journal-title":"Radiologic Technol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2015.02.002","article-title":"Adrenal steroidogenesis and congenital adrenal hyperplasia","volume":"44","author":"Turcu","year":"2015","journal-title":"Endocrinol Metab Clinics North America"},{"key":"B8","doi-asserted-by":"publisher","first-page":"105360","DOI":"10.1016\/j.jsbmb.2019.04.009","article-title":"Rna-seq analysis of lps-induced transcriptional changes and its possible implications for the adrenal gland dysregulation during sepsis","volume":"191","author":"Chen","year":"2019","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200509-1369OC","article-title":"Diagnosis of adrenal insufficiency in severe sepsis and septic shock","volume":"174","author":"Annane","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e32818a6d74","article-title":"Mechanisms and clinical consequences of critical illness associated adrenal insufficiency","volume":"13","author":"Marik","year":"2007","journal-title":"Curr Opin Crit Care"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31825fec26","article-title":"Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis*","volume":"40","author":"Chan","year":"2012","journal-title":"Crit Care Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2014.12.019","article-title":"The role of adrenal gland microenvironment in the hpa axis function and dysfunction during sepsis","volume":"408","author":"Kanczkowski","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/ccm.0000000000001373","article-title":"Mortality of septic mice strongly correlates with adrenal gland inflammation","volume":"44","author":"Jennewein","year":"2016","journal-title":"Crit Care Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00156","article-title":"Adrenal gland microenvironment and its involvement in the regulation of stress-induced hormone secretion during sepsis","volume":"7","author":"Kanczkowski","year":"2016","journal-title":"Front Endocrinol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.670574","article-title":"Single-cell transcriptional heterogeneity of neutrophils during acute pulmonary cryptococcus neoformans infection","volume":"12","author":"Deerhake","year":"2021","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","article-title":"Doubletfinder: Doublet detection in single-cell rna sequencing data using artificial nearest neighbors","volume":"8","author":"McGinnis","year":"2019","journal-title":"Cell Syst"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4091","article-title":"Batch effects in single-cell rna-sequencing data are corrected by matching mutual nearest neighbors","volume":"36","author":"Haghverdi","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/s13619-020-00042-8","article-title":"Mapping a mammalian adult adrenal gland hierarchy across species by microwell-seq","volume":"9","author":"Lai","year":"2020","journal-title":"Cell regeneration (London England)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022350118","article-title":"Single-cell atlas of developing murine adrenal gland reveals relation of schwann cell precursor signature to neuroblastoma phenotype","volume":"118","author":"Hanemaaijer","year":"2021","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B22","doi-asserted-by":"publisher","first-page":"5309","DOI":"10.1038\/s41467-021-24870-7","article-title":"Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors","volume":"12","author":"Bedoya-Reina","year":"2021","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","article-title":"Gsva: Gene set variation analysis for microarray and rna-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat Biotechnol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0292-x","article-title":"Cellphonedb: Inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes","volume":"15","author":"Efremova","year":"2020","journal-title":"Nat Protoc"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1694","article-title":"Synergistic activation of steroidogenic acute regulatory protein expression and steroid biosynthesis by retinoids: Involvement of Camp\/Pka signaling","volume":"155","author":"Manna","year":"2014","journal-title":"Endocrinology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081865","article-title":"Cell proliferation, movement and differentiation during maintenance of the adult mouse adrenal cortex","volume":"8","author":"Chang","year":"2013","journal-title":"PloS One"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.561370","article-title":"Adropin stimulates proliferation and inhibits adrenocortical steroidogenesis in the human adrenal carcinoma (Hac15) cell line","volume":"11","author":"Stelcer","year":"2020","journal-title":"Front Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200704059","article-title":"The mitochondrial respiratory chain is a modulator of apoptosis","volume":"179","author":"Kwong","year":"2007","journal-title":"J Cell Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-061214-111754","article-title":"Hedgehog signaling and steroidogenesis","volume":"77","author":"Finco","year":"2015","journal-title":"Annu Rev Physiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-03061","article-title":"Sonic hedgehog and wnt signaling promote adrenal gland regeneration in Male mice","volume":"159","author":"Finco","year":"2018","journal-title":"Endocrinology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.19.2.0326","article-title":"Intraadrenal interactions in the regulation of adrenocortical steroidogenesis","volume":"19","author":"Ehrhart-Bornstein","year":"1998","journal-title":"Endocrine Rev"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.01.022","article-title":"Egfl7 regulates sprouting angiogenesis and endothelial integrity in a human blood vessel model","volume":"197","author":"Usuba","year":"2019","journal-title":"Biomaterials"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.04.022","article-title":"Egfl7 mediates Bmp9-induced sprouting angiogenesis of endothelial cells derived from human embryonic stem cells","volume":"12","author":"Richter","year":"2019","journal-title":"Stem Cell Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4614-8289-5_1","article-title":"Gadd45 in stress signaling, cell cycle control, and apoptosis","volume":"793","author":"Salvador","year":"2013","journal-title":"Adv Exp Med Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6647","article-title":"\u03a3-1 receptor stimulation protects against pressure-induced damage through insr-mapk signaling in human trabecular meshwork cells","volume":"16","author":"Meng","year":"2017","journal-title":"Mol Med Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1884","article-title":"Oncogenic functions of Igf1r and insr in prostate cancer include enhanced tumor growth, cell migration and angiogenesis","volume":"5","author":"Heidegger","year":"2014","journal-title":"Oncotarget"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-013-1532-y","article-title":"Histaminylation of fibrinogen by tissue transglutaminase-2 (Tgm-2): Potential role in modulating inflammation","volume":"45","author":"Lai","year":"2013","journal-title":"Amino Acids"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.308","article-title":"Carboxypeptidase e: A negative regulator of the canonical wnt signaling pathway","volume":"32","author":"Skalka","year":"2013","journal-title":"Oncogene"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2010.12.018","article-title":"Protective effect of rat aldo-keto reductase (Akr1c15) on endothelial cell damage elicited by 4-Hydroxy-2-Nonenal","volume":"191","author":"Matsunaga","year":"2011","journal-title":"Chemico-biological Interact"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051006","article-title":"Distinct populations of macrophages in the adult rat adrenal gland: A subpopulation with neurotrophin-4-Like immunoreactivity","volume":"291","author":"Schober","year":"1998","journal-title":"Cell Tissue Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/bf00414161","article-title":"Macrophages within the human adrenal gland","volume":"278","author":"Gonz\u00e1lez-Hern\u00e1ndez","year":"1994","journal-title":"Cell Tissue Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.11.6110","article-title":"Lymphocytes stimulate dehydroepiandrosterone production through direct cellular contact with adrenal zona reticularis cells: A novel mechanism of immune-endocrine interaction","volume":"84","author":"Wolkersd\u00f6rfer","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.12.020","article-title":"Characterization of the lps-induced inflammation of the adrenal gland in mice","volume":"371","author":"Kanczkowski","year":"2013","journal-title":"Mol Cell Endocrinol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.1.275","article-title":"Pu.1 regulates cathepsin s expression in professional apcs","volume":"176","author":"Wang","year":"2006","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.11.006","article-title":"Expanding roles for gilt in immunity","volume":"25","author":"West","year":"2013","journal-title":"Curr Opin Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1210\/endo-129-1-53","article-title":"Interleukin-1 beta enhances corticosterone secretion by acting directly on the rat adrenal gland","volume":"129","author":"Andreis","year":"1991","journal-title":"Endocrinology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.04.018","article-title":"Interleukins 1\u03b1 and 1\u03b2 as regulators of steroidogenesis in human nci-H295r adrenocortical cells","volume":"76","author":"Tkachenko","year":"2011","journal-title":"Steroids"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharma.2015.09.002","article-title":"Lp-Pla2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques","volume":"74","author":"Bonnefont-Rousselot","year":"2016","journal-title":"Annales Pharm francaises"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8010040","article-title":"Candida albicans at host barrier sites: Pattern recognition receptors and beyond","volume":"8","author":"Swidergall","year":"2019","journal-title":"Pathog (Basel Switzerland)"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and regulation of Nlrp3 inflammasome activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem Sci"},{"key":"B52","doi-asserted-by":"publisher","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.75523","article-title":"Progressive axonopathy when oligodendrocytes lack the myelin protein Cmtm5","volume":"11","author":"Buscham","year":"2022","journal-title":"eLife"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00547","article-title":"Acth action on star biology","volume":"10","author":"Clark","year":"2016","journal-title":"Front Neurosci"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.11.012","article-title":"Adrenocortical stem and progenitor cells: Unifying model of two proposed origins","volume":"336","author":"Wood","year":"2011","journal-title":"Mol Cell Endocrinol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.4161\/org.7.4.18060","article-title":"Transition from organogenesis to stem cell maintenance in the mouse adrenal cortex","volume":"7","author":"Chang","year":"2011","journal-title":"Organogenesis"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(94)90266-6","article-title":"Cloning of acth-regulated genes in the adrenal cortex","volume":"49","author":"Raikhinstein","year":"1994","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00031.2005","article-title":"Zone-specific cell proliferation during adrenocortical regeneration after enucleation in rats","volume":"289","author":"Ennen","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/nature12345","article-title":"Lrg1 promotes angiogenesis by modulating endothelial tgf-B signalling","volume":"499","author":"Wang","year":"2013","journal-title":"Nature"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107927","article-title":"The role of Cd71(+) erythroid cells in the regulation of the immune response","volume":"228","author":"Grzywa","year":"2021","journal-title":"Pharmacol Ther"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.01.003","article-title":"Neglected cells: Immunomodulatory roles of Cd71(+) erythroid cells","volume":"40","author":"Elahi","year":"2019","journal-title":"Trends Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.830025","article-title":"Cd71(+) erythroid cell expansion in adult sepsis: Potential causes and role in prognosis and nosocomial infection prediction","volume":"13","author":"Zhao","year":"2022","journal-title":"Front Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(06)69005-3","article-title":"Neutrophils in development of multiple organ failure in sepsis","volume":"368","author":"Brown","year":"2006","journal-title":"Lancet (London England)"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/nm1565","article-title":"Platelet Tlr4 activates neutrophil extracellular traps to ensnare bacteria in septic blood","volume":"13","author":"Clark","year":"2007","journal-title":"Nat Med"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.05.002","article-title":"An essential role for the Nlrp3 inflammasome in host defense against the human fungal pathogen candida albicans","volume":"5","author":"Hise","year":"2009","journal-title":"Cell Host Microbe"},{"key":"B66","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/s0162-3109(97)00057-x","article-title":"Controlling the complement system in inflammation","volume":"38","author":"Kirschfink","year":"1997","journal-title":"Immunopharmacology"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0377-2","article-title":"Card9(+) microglia promote antifungal immunity Via il-1\u03b2- and Cxcl1-mediated neutrophil recruitment","volume":"20","author":"Drummond","year":"2019","journal-title":"Nat Immunol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00039","article-title":"Mechanistic insights into the role of c-type lectin Receptor\/Card9 signaling in human antifungal immunity","volume":"6","author":"Drummond","year":"2016","journal-title":"Front Cell Infect Microbiol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0170","article-title":"Immune cells and cytokine circuits: Toward a working model for understanding direct immune-to-Adrenal communication pathways","volume":"149","author":"Deak","year":"2008","journal-title":"Endocrinology"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060890","article-title":"Nadph oxidases (Nox): An overview from discovery, molecular mechanisms to physiology and pathology","volume":"10","author":"Vermot","year":"2021","journal-title":"Antioxidants (Basel Switzerland)"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002560","article-title":"The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis","volume":"3","author":"Flierl","year":"2008","journal-title":"PloS One"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/nm1753","article-title":"Functional roles for C5a receptors in sepsis","volume":"14","author":"Rittirsch","year":"2008","journal-title":"Nat Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00592","article-title":"C1 complex: An adaptable proteolytic module for complement and non-complement functions","volume":"8","author":"Lu","year":"2017","journal-title":"Front Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00364","article-title":"Il33: Roles in allergic inflammation and therapeutic perspectives","volume":"10","author":"Chan","year":"2019","journal-title":"Front Immunol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1096\/fj.01-0245com","article-title":"Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells","volume":"16","author":"Galon","year":"2002","journal-title":"FASEB J Off Publ Fed Am Societies Exp Biol"},{"key":"B76","article-title":"Migration inhibitory factor expression in experimentally induced endotoxemia","volume":"150","author":"Bacher","year":"1997","journal-title":"Am J Pathol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13881","article-title":"Complement in sepsis-when science meets clinics","volume":"594","author":"Mollnes","year":"2020","journal-title":"FEBS Lett"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.966814\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:05:39Z","timestamp":1667282739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.966814\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":77,"alternative-id":["10.3389\/fimmu.2022.966814"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.966814","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]},"article-number":"966814"}}