{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:26:57Z","timestamp":1776482817940,"version":"3.51.2"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009193","name":"Marsden Fund","doi-asserted-by":"publisher","award":["UOA2007"],"award-info":[{"award-number":["UOA2007"]}],"id":[{"id":"10.13039\/501100009193","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human pathogen <jats:italic>Streptococcus pyogenes<\/jats:italic>, or Group A Streptococcus (GAS), is associated with a variety of diseases ranging from mild skin and soft tissue infections to invasive diseases and immune sequelae such as rheumatic heart disease. We have recently reported that one of the virulence factors of this pathogen, the pilus, has inflammatory properties and strongly stimulates the innate immune system. Here we used a range of nonpathogenic <jats:italic>Lactococcus lactis<\/jats:italic> gain\u2010of\u2010function mutants, each expressing one of the major pilus types of GAS, to compare the immune responses generated by various types of fully assembled pili. <jats:italic>In vitro<\/jats:italic> assays indicated variability in the inflammatory response induced by different pili, with the fibronectin\u2010binding, collagen\u2010binding, T antigen (FCT)\u20101\u2010type pilus from GAS serotype M6\/T6 inducing significantly stronger cytokine secretion than other pili. Furthermore, we established that the same trend of pili\u2010mediated immune response could be modeled in <jats:italic>Galleria mellonella<\/jats:italic> larvae, which possess a similar innate immune system to vertebrates. Counterintuitively, across the panel of pili types examined in this study, we observed a negative correlation between the intensity of the immune response demonstrated in our experiments and the disease severity observed clinically in the GAS strains associated with each pilus type. This observation suggests that pili\u2010mediated inflammation is more likely to promote bacterial clearance instead of causing disruptive damages that intensify pathogenesis. This also indicates that pili may not be the main contributor to the inflammatory symptoms seen in GAS diseases. Rather, the immune\u2010potentiating properties of the pilus components could potentially be exploited as a vaccine adjuvant.<\/jats:p>","DOI":"10.1111\/imcb.12692","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T19:44:11Z","timestamp":1696535051000},"page":"21-33","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Different Group A Streptococcus pili lead to varying proinflammatory cytokine responses and virulence"],"prefix":"10.1111","volume":"102","author":[{"given":"Risa","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-090X","authenticated-orcid":false,"given":"Adrina Hema","family":"J\u2010Khemlani","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-1215","authenticated-orcid":false,"given":"Jacelyn Mei San","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery The University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-6927","authenticated-orcid":false,"given":"Fiona Jane","family":"Radcliff","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine &amp; Pathology, School of Medical Sciences The University of Auckland  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