{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:11:23Z","timestamp":1790827883288,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI101055, AI119566, AI117095, AI135465, AI137778, AI141372, AI140035"],"award-info":[{"award-number":["AI101055, AI119566, AI117095, AI135465, AI137778, AI141372, AI140035"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, both local and systemic. Predominant among these toxins is pertussis toxin (PT), a multi-subunit protein toxin that inhibits signaling through a subset of G protein-coupled receptors in mammalian cells. PT activity has been linked with severe and lethal pertussis disease in young infants and a detoxified version of PT is a common component of all licensed acellular pertussis vaccines. The role of PT in typical pertussis disease in other individuals is less clear, but significant evidence supporting its contribution to pathogenesis has been accumulated from animal model studies. In this review we discuss the evidence indicating a role for PT in pertussis disease, focusing on its contribution to severe pertussis in infants, modulation of immune and inflammatory responses to infection, and the characteristic paroxysmal cough of pertussis.<\/jats:p>","DOI":"10.3390\/toxins11070373","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T08:19:13Z","timestamp":1561623553000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Association of Pertussis Toxin with Severe Pertussis Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Karen","family":"Scanlon","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciaran","family":"Skerry","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Carbonetti","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ftv073","DOI":"10.1093\/femspd\/ftv073","article-title":"Contribution of pertussis toxin to the pathogenesis of pertussis disease","volume":"73","author":"Carbonetti","year":"2015","journal-title":"Pathog. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1097\/00006454-198409000-00019","article-title":"The concept of pertussis as a toxin-mediated disease","volume":"3","author":"Pittman","year":"1984","journal-title":"Pediatr. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/infdis\/150.2.219","article-title":"Pertussis toxin and extracytoplasmic adenylate cyclase as virulence factors of Bordetella pertussis","volume":"150","author":"Weiss","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3757","DOI":"10.1128\/iai.57.12.3757-3764.1989","article-title":"Lethal infection by Bordetella pertussis mutants in the infant mouse model","volume":"57","author":"Weiss","year":"1989","journal-title":"Infect. Immun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1128\/iai.58.10.3445-3447.1990","article-title":"Adenylate cyclase toxin is critical for colonization and pertussis toxin is critical for lethal infection by Bordetella pertussis in infant mice","volume":"58","author":"Goodwin","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_6","unstructured":"Centers for Disease Control and Prevention (2019, May 14). 2018 Provisional Pertussis Surveillance Report, Available online: https:\/\/www.cdc.gov\/pertussis\/downloads\/pertuss-surv-report-2018-508.pdf."},{"key":"ref_7","unstructured":"Centers for Disease Control and Prevention (2019, May 14). Pertussis (Whooping Cough): Complications, Available online: https:\/\/www.cdc.gov\/pertussis\/about\/complications.html."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/PCC.0b013e31828a70fe","article-title":"Critical pertussis illness in children: A multicenter prospective cohort study","volume":"14","author":"Berger","year":"2013","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1097\/01.PCC.0000265499.50592.37","article-title":"Pertussis: Severe clinical presentation in pediatric intensive care and its relation to outcome","volume":"8","author":"Namachivayam","year":"2007","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jpids\/pis105","article-title":"Characteristics of Severe Bordetella pertussis Infection Among Infants \u226490 Days of Age Admitted to Pediatric Intensive Care Units\u2013Southern California, September 2009\u2013June 2011","volume":"2","author":"Murray","year":"2013","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/cid\/civ472","article-title":"Risk Factors Associated With Infant Deaths From Pertussis: A Case-Control Study","volume":"61","author":"Winter","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.3389\/fimmu.2018.01918","article-title":"Energy Demands of Early Life Drive a Disease Tolerant Phenotype and Dictate Outcome in Neonatal Bacterial Sepsis","volume":"9","author":"Harbeson","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1469-0691.2010.03255.x","article-title":"Marked difference between adults and children in Bordetella pertussis DNA load in nasopharyngeal swabs","volume":"17","author":"Nakamura","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1007\/s001340000587","article-title":"Is leukocytosis a predictor of mortality in severe pertussis infection?","volume":"26","author":"Pierce","year":"2000","journal-title":"Intensive Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"190","DOI":"10.14745\/ccdr.v44i09a01","article-title":"Clinical characteristics of pediatric pertussis cases, Quebec 2015\u20132017","volume":"44","author":"Desjardins","year":"2018","journal-title":"Can. Commun. Dis. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1002\/ppul.21082","article-title":"Fulminant pertussis: A multi-center study with new insights into the clinico-pathological mechanisms","volume":"44","author":"Sawal","year":"2009","journal-title":"Pediatr. Pulmonol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1084\/jem.125.4.619","article-title":"Studies on the leukocytosis and lymphocytosis induced by Bordetella pertussis. II. The effect of pertussis vaccine on the thoracic duct lymph and lymphocytes of mice","volume":"125","author":"Morse","year":"1967","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"ftw087","DOI":"10.1093\/femspd\/ftw087","article-title":"Pertussis leukocytosis: Mechanisms, clinical relevance and treatment","volume":"74","author":"Carbonetti","year":"2016","journal-title":"Pathog. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/00000441-194210000-00009","article-title":"The tolerance of rabbits for the agglutinogen and the toxins of Haemophilus pertussis","volume":"204","author":"Ehrich","year":"1942","journal-title":"Am. J. Med Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1542\/peds.18.1.64","article-title":"Effect of extracts of Hemophilus pertussis on leukocyte counts in normal and sensitized mice","volume":"18","author":"Bradford","year":"1956","journal-title":"Pediatrics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1084\/jem.143.6.1483","article-title":"Isolation and properties of the leukocytosis- and lymphocytosis-promoting factor of Bordetella pertussis","volume":"143","author":"Morse","year":"1976","journal-title":"J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1073\/pnas.79.10.3129","article-title":"Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein","volume":"79","author":"Katada","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1016\/S0021-9258(18)32863-1","article-title":"Loss of the inhibitory function of the guanine nucleotide regulatory component of adenylate cyclase due to its ADP ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes","volume":"258","author":"Murayama","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/infdis\/165.5.945","article-title":"Effect of pertussis toxin on susceptibility of infant rats to Haemophilus influenzae type b","volume":"165","author":"Samore","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1128\/IAI.73.6.3636-3645.2005","article-title":"Infection of newborn piglets with Bordetella pertussis: A new model for pertussis","volume":"73","author":"Elahi","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1600-0684.1996.tb00032.x","article-title":"Pertussis toxin induces lymphocytosis in rhesus macaques","volume":"25","author":"Hinds","year":"1996","journal-title":"J. Med. Primatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/aid.1997.13.87","article-title":"The lymphocytosis-promoting agent pertussis toxin affects virus burden and lymphocyte distribution in the SIV-infected rhesus macaque","volume":"13","author":"Pauza","year":"1997","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1084\/jem.187.2.205","article-title":"Molecular mechanisms of lymphocyte homing to peripheral lymph nodes","volume":"187","author":"Warnock","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3109\/15419069909010801","article-title":"Pertussis toxin treatment in vivo reduces surface expression of the adhesion integrin leukocyte function antigen-1 (LFA-1)","volume":"7","author":"Schenkel","year":"1999","journal-title":"Cell Adhes. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1046\/j.1440-1843.2003.00459.x","article-title":"A marked decrease in L-selectin expression by leucocytes in infants with Bordetella pertussis infection: Leucocytosis explained?","volume":"8","author":"Hodge","year":"2003","journal-title":"Respirology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1309\/BANX-8JKM-TUQN-4D6P","article-title":"Marked increase in L-selectin-negative T cells in neonatal pertussis. The lymphocytosis explained?","volume":"114","author":"Hudnall","year":"2000","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6034","DOI":"10.1016\/j.vaccine.2009.07.074","article-title":"First report and detailed characterization of B. pertussis isolates not expressing Pertussis Toxin or Pertactin","volume":"27","author":"Bouchez","year":"2009","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3201\/eid2202.151332","article-title":"Bordetella pertussis Strain Lacking Pertactin and Pertussis Toxin","volume":"22","author":"Williams","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mielcarek, N., Debrie, A.S., Raze, D., Bertout, J., Rouanet, C., Younes, A.B., Creusy, C., Engle, J., Goldman, W.E., and Locht, C. (2006). Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020065"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Thorstensson, R., Trollfors, B., Al-Tawil, N., Jahnmatz, M., Bergstrom, J., Ljungman, M., Torner, A., Wehlin, L., Van Broekhoven, A., and Bosman, F. (2014). A phase I clinical study of a live attenuated Bordetella pertussis vaccine-BPZE1; a single centre, double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally to healthy adult male volunteers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0083449"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/infdis\/jix254","article-title":"Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection","volume":"216","author":"Locht","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1128\/IAI.06310-11","article-title":"Nonhuman primate model of pertussis","volume":"80","author":"Warfel","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1097\/00006454-199404000-00011","article-title":"Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis","volume":"13","author":"Heininger","year":"1994","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1128\/iai.31.3.1223-1231.1981","article-title":"Role of antibody to leukocytosis-promoting factor hemagglutinin and to filamentous hemagglutinin in immunity to pertussis","volume":"31","author":"Sato","year":"1981","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1093\/infdis\/150.6.823","article-title":"Protective activities of the filamentous hemagglutinin and the lymphocytosis-promoting factor of Bordetella pertussis in mice","volume":"150","author":"Oda","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1128\/iai.46.2.422-428.1984","article-title":"Monoclonal antibody against pertussis toxin: Effect on toxin activity and pertussis infections","volume":"46","author":"Sato","year":"1984","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1128\/iai.58.10.3369-3374.1990","article-title":"Protective activities in mice of monoclonal antibodies against pertussis toxin","volume":"58","author":"Sato","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1128\/CDLI.6.4.464-470.1999","article-title":"Protective effects of pertussis immunoglobulin (P-IGIV) in the aerosol challenge model","volume":"6","author":"Bruss","year":"1999","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1097\/00006454-199906000-00006","article-title":"Treatment of severe pertussis: A study of the safety and pharmacology of intravenous pertussis immunoglobulin","volume":"18","author":"Bruss","year":"1999","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"316ra195","DOI":"10.1126\/scitranslmed.aad0966","article-title":"A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough","volume":"7","author":"Nguyen","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1136\/adc.86.6.453-a","article-title":"Bordetella pertussis infection causing pulmonary hypertension","volume":"86","author":"Casano","year":"2002","journal-title":"Arch. Dis. Child."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/00365540510026436","article-title":"Pertussis and fatal pulmonary hypertension: A discouraged entity","volume":"37","author":"Donoso","year":"2005","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1086\/589753","article-title":"Pathology and pathogenesis of fatal Bordetella pertussis infection in infants","volume":"47","author":"Paddock","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1542\/peds.112.6.1274","article-title":"Fatal pulmonary hypertension associated with pertussis in infants: Does extracorporeal membrane oxygenation have a role?","volume":"112","author":"Halasa","year":"2003","journal-title":"Pediatrics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e8823","DOI":"10.1097\/MD.0000000000008823","article-title":"Severe pertussis infection: A clinicopathological study","volume":"96","author":"Palvo","year":"2017","journal-title":"Medicine (Baltim.)"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"134S","DOI":"10.1016\/j.amjhyper.2005.05.005","article-title":"How to explain the differences between renin angiotensin system modulators","volume":"18","author":"Levy","year":"2005","journal-title":"Am. J. Hypertens"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/0006-291X(91)91723-P","article-title":"Changes in expression of angiotensin receptor subtypes in the rat aorta during development","volume":"179","author":"Viswanathan","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1007\/s004670050067","article-title":"Expression of renal and vascular angiotensin II receptor subtypes in children","volume":"14","author":"Viswanathan","year":"2000","journal-title":"Pediatr. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1006\/bbrc.1996.1661","article-title":"The angiotensin II type 2 receptor primarily inhibits cell growth via pertussis toxin-sensitive G proteins","volume":"228","author":"Ozawa","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0014-2999(93)90415-E","article-title":"Cholera toxin but not pertussis toxin inhibits angiotensin II-enhanced contractions in the rat portal vein","volume":"230","author":"Zhang","year":"1993","journal-title":"Eur. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eaat1631","DOI":"10.1126\/scisignal.aat1631","article-title":"Functional selectivity profiling of the angiotensin II type 1 receptor using pathway-wide BRET signaling sensors","volume":"11","author":"Namkung","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1172\/JCI5182","article-title":"Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth","volume":"103","author":"Akishita","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1542\/peds.97.5.607","article-title":"Pertussis deaths: Report of 23 cases in the United States, 1992 and 1993","volume":"97","author":"Wortis","year":"1996","journal-title":"Pediatrics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1128\/CMR.00083-15","article-title":"Pertussis: Microbiology, Disease, Treatment, and Prevention","volume":"29","author":"Kilgore","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1136\/adc.63.6.598","article-title":"Severe hypoxaemia in pertussis","volume":"63","author":"Southall","year":"1988","journal-title":"Arch. Dis. Child."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nm.3407","article-title":"Development, maintenance and disruption of the blood-brain barrier","volume":"19","author":"Obermeier","year":"2013","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/j.1462-5822.2006.00813.x","article-title":"Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model","volume":"9","author":"Kugler","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e00355-17","DOI":"10.1128\/IAI.00355-17","article-title":"Fatal pertussis in the neonatal mouse model is associated with pertussis toxin-mediated pathology beyond the airways","volume":"85","author":"Scanlon","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ccr3.765","article-title":"Recurrent apnea in an infant with pertussis due to household transmission","volume":"5","author":"Ochi","year":"2017","journal-title":"Clin. Case Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1172\/JCI117257","article-title":"Pertussis toxin treatment alters manganese superoxide dismutase activity in lung. Evidence for lung oxygen toxicity in air-breathing rats","volume":"93","author":"Clerch","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1165\/ajrcmb.20.3.3373","article-title":"Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C","volume":"20","author":"Tsan","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1128\/IAI.74.5.2619-2627.2006","article-title":"Maternal immunity provides protection against pertussis in newborn piglets","volume":"74","author":"Elahi","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1099\/00222615-40-3-205","article-title":"Cough production, leucocytosis and serology of rats infected intrabronchially with Bordetella pertussis","volume":"40","author":"Hall","year":"1994","journal-title":"J. Med. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/infdis\/142.1.56","article-title":"Bordetella pertussis respiratory tract infection in the mouse: Pathophysiological responses","volume":"142","author":"Pittman","year":"1980","journal-title":"J. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0163-4453(80)90650-7","article-title":"Experimental pertussis infection in the rabbit: Similarities with infection in primates","volume":"2","author":"Preston","year":"1980","journal-title":"J. Infect."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"ftv067","DOI":"10.1093\/femspd\/ftv067","article-title":"Roads to the development of improved pertussis vaccines paved by immunology","volume":"73","author":"Brummelman","year":"2015","journal-title":"Pathog. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"21629","DOI":"10.1074\/jbc.273.34.21629","article-title":"Involvement of Galphai2 in the maintenance and biogenesis of epithelial cell tight junctions","volume":"273","author":"Saha","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1128\/IAI.01578-06","article-title":"Pertussis toxin targets airway macrophages to promote Bordetella pertussis infection of the respiratory tract","volume":"75","author":"Carbonetti","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.1128\/IAI.69.12.7635-7641.2001","article-title":"Pertussis toxin and lipopolysaccharide influence phagocytosis of Bordetella pertussis by human monocytes","volume":"69","author":"Schaeffer","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1128\/IAI.01150-08","article-title":"Role of neutrophils in response to Bordetella pertussis infection in mice","volume":"77","author":"Andreasen","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5139","DOI":"10.1128\/IAI.00895-08","article-title":"Pertussis toxin inhibits early chemokine production to delay neutrophil recruitment in response to Bordetella pertussis respiratory tract infection in mice","volume":"76","author":"Andreasen","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Andreasen, C., Powell, D.A., and Carbonetti, N.H. (2009). Pertussis toxin stimulates IL-17 production in response to Bordetella pertussis infection in mice. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007079"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1128\/CVI.00695-14","article-title":"Identification of pertussis-specific effector memory T cells in preschool children","volume":"22","author":"Schure","year":"2015","journal-title":"Clin. Vaccine Immunol. CVI"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1084\/jem.186.11.1843","article-title":"Atypical disease after Bordetella pertussis respiratory infection of mice with targeted disruptions of interferon-gamma receptor or immunoglobulin mu chain genes","volume":"186","author":"Mahon","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1128\/iai.61.2.399-410.1993","article-title":"Cell-mediated immunity to Bordetella pertussis: Role of Th1 cells in bacterial clearance in a murine respiratory infection model","volume":"61","author":"Mills","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1128\/IAI.72.6.3350-3358.2004","article-title":"Suppression of serum antibody responses by pertussis toxin after respiratory tract colonization by Bordetella pertussis and identification of an immunodominant lipoprotein","volume":"72","author":"Carbonetti","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/intimm\/10.5.651","article-title":"Pertussis toxin potentiates Th1 and Th2 responses to co-injected antigen: Adjuvant action is associated with enhanced regulatory cytokine production and expression of the co-stimulatory molecules B7-1, B7-2 and CD28","volume":"10","author":"Ryan","year":"1998","journal-title":"Int. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1128\/IAI.71.4.1719-1724.2003","article-title":"Role of antibodies in immunity to Bordetella infections","volume":"71","author":"Kirimanjeswara","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.1172\/JCI24609","article-title":"Pertussis toxin inhibits neutrophil recruitment to delay antibody-mediated clearance of Bordetella pertussis","volume":"115","author":"Kirimanjeswara","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1126\/science.3095921","article-title":"Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide","volume":"234","author":"Jakway","year":"1986","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.4049\/jimmunol.135.6.4135","article-title":"Inhibition of lymphocyte and neutrophil chemotaxis by pertussis toxin","volume":"135","author":"Spangrude","year":"1985","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1128\/iai.49.1.90-97.1985","article-title":"Immune suppression and induction of gamma interferon by pertussis toxin","volume":"49","author":"Vogel","year":"1985","journal-title":"Infect. Immun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.immuni.2018.07.015","article-title":"Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution","volume":"49","author":"Proto","year":"2018","journal-title":"Immunity"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/eji.200535353","article-title":"Pertussis toxin as an adjuvant suppresses the number and function of CD4+CD25+ T regulatory cells","volume":"36","author":"Chen","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"206","DOI":"10.4049\/jimmunol.1101537","article-title":"Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatory activities","volume":"188","author":"Fujii","year":"2012","journal-title":"J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1172\/JCI97943","article-title":"Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators","volume":"128","author":"Serhan","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1017\/S1462399409000957","article-title":"Emerging role of the cannabinoid receptor CB2 in immune regulation: Therapeutic prospects for neuroinflammation","volume":"11","author":"Cabral","year":"2009","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1128\/IAI.00808-12","article-title":"Pertussis toxin exacerbates and prolongs airway inflammatory responses during Bordetella pertussis infection","volume":"80","author":"Connelly","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_94","first-page":"278","article-title":"Reduction of Pertussis Inflammatory Pathology by Therapeutic Treatment With Sphingosine-1-Phosphate Receptor Ligands by a Pertussis Toxin-Insensitive Mechanism","volume":"215","author":"Skerry","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/infdis\/jiu823","article-title":"Sphingosine-1-phosphate Receptor Agonism Reduces Bordetella pertussis-mediated Lung Pathology","volume":"211","author":"Skerry","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e018594","DOI":"10.1136\/bmjopen-2017-018594","article-title":"Investigating Bordetella pertussis colonisation and immunity: Protocol for an inpatient controlled human infection model","volume":"7","author":"Gbesemete","year":"2017","journal-title":"BMJ Open"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.3389\/fimmu.2018.02872","article-title":"Non-specific Effects of Live Attenuated Pertussis Vaccine Against Heterologous Infectious and Inflammatory Diseases","volume":"9","author":"Cauchi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.4161\/hv.29576","article-title":"Licensed pertussis vaccines in the United States. History and current state","volume":"10","author":"Klein","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1016\/j.vaccine.2013.08.034","article-title":"Experience with monocomponent acellular pertussis combination vaccines for infants, children, adolescents and adults\u2014A review of safety, immunogenicity, efficacy and effectiveness studies and 15 years of field experience","volume":"31","author":"Dalby","year":"2013","journal-title":"Vaccine"},{"key":"ref_100","first-page":"CD001478","article-title":"Acellular vaccines for preventing whooping cough in children","volume":"9","author":"Zhang","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_101","first-page":"30334","article-title":"Epidemiology of pertussis in Denmark, 1995 to 2013","volume":"21","author":"Dalby","year":"2016","journal-title":"Euro Surveill. Bull. Eur. Mal. Transm. Eur. Commun. Dis. Bull."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"S119","DOI":"10.1093\/cid\/ciw550","article-title":"Pertussis in Young Infants Throughout the World","volume":"63","author":"Cherry","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1099\/00222615-40-5-307","article-title":"Responses to Bordetella pertussis mutant strains and to vaccination in the coughing rat model of pertussis","volume":"40","author":"Parton","year":"1994","journal-title":"J. Med. Microbiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1586\/14760584.2014.946016","article-title":"The baboon model of pertussis: Effective use and lessons for pertussis vaccines","volume":"13","author":"Warfel","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/infdis\/jiy022","article-title":"Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough","volume":"217","author":"Kapil","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1007\/s00408-009-9196-9","article-title":"Coughing precipitated by Bordetella pertussis infection","volume":"188","author":"Hewitt","year":"2010","journal-title":"Lung"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1620\/tjem.130.105","article-title":"Effects of islet-activating protein (IAP) on blood glucose and plasma insulin in healthy volunteers (phase 1 studies)","volume":"130","author":"Toyota","year":"1980","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1128\/IAI.02222-14","article-title":"Epithelial anion transporter pendrin contributes to inflammatory lung pathology in mouse models of Bordetella pertussis infection","volume":"82","author":"Scanlon","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e00601-18","DOI":"10.1128\/IAI.00601-18","article-title":"Peptidoglycan Recognition Protein 4 Suppresses Early Inflammatory Responses to Bordetella pertussis and Contributes to Sphingosine-1-Phosphate Receptor Agonist-Mediated Disease Attenuation","volume":"87","author":"Skerry","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_110","first-page":"253","article-title":"The mechanism for the rapid desensitization in bradykinin-stimulated inositol monophosphate production in NG108-15 cells involves interaction of a single receptor with multiple signaling pathways","volume":"266","author":"Wolsing","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1111\/j.1471-4159.2006.04320.x","article-title":"Molecular cloning of prostaglandin EP3 receptors from canine sensory ganglia and their facilitatory action on bradykinin-induced mobilization of intracellular calcium","volume":"100","author":"Kozaki","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.coph.2011.06.005","article-title":"G-protein coupled receptors regulating cough","volume":"11","author":"Maher","year":"2011","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1128\/IAI.71.11.6358-6366.2003","article-title":"Pertussis toxin plays an early role in respiratory tract colonization by Bordetella pertussis","volume":"71","author":"Carbonetti","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/01.inf.0000247103.01075.cc","article-title":"Is pertussis immune globulin efficacious for the treatment of hospitalized infants with pertussis? No answer yet","volume":"26","author":"Halperin","year":"2007","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Ernst, K., Eberhardt, N., Mittler, A.K., Sonnabend, M., Anastasia, A., Freisinger, S., Schiene-Fischer, C., Malesevic, M., and Barth, H. (2018). Pharmacological Cyclophilin Inhibitors Prevent Intoxication of Mammalian Cells with Bordetella pertussis Toxin. Toxins, 10.","DOI":"10.3390\/toxins10050181"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/7\/373\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:01:35Z","timestamp":1760187695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/7\/373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,27]]},"references-count":115,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["toxins11070373"],"URL":"https:\/\/doi.org\/10.3390\/toxins11070373","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,27]]}}}