{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:55:07Z","timestamp":1776318907099,"version":"3.50.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Group B\n                      <jats:italic>Streptococcus<\/jats:italic>\n                      (GBS) remains a leading cause of neonatal sepsis and meningitis despite preventive strategies. Disease severity and clinical presentation vary widely and are influenced by strain-specific virulence traits. Macrophages are key innate immune sentinels during GBS infection; however, how genetically distinct clinical isolates differentially and dynamically reprogram macrophage inflammatory, immunoregulatory, metabolic, and cell death responses remains poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human THP-1 macrophages were infected with 12 fully characterized clinical GBS isolates representing multiple serotypes, sequence types, clinical presentations, and neonatal gestational ages. Cytokine and chemokine production was quantified at 3 and 24 hours post-infection using LEGENDplex bead-based immunoassays. Caspase-1 activity was measured by bioluminescence, and expression of inflammatory, immunoregulatory, metabolic, and cell death\u2013associated genes were assessed by RT-qPCR at 4 and 24 hours. Data were analyzed using appropriate statistical tests, and multidimensional responses were integrated using radar plot visualization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Macrophage responses to GBS were highly isolate-specific and varied over time. Serotype Ia and Ib isolates triggered rapid inflammasome-associated activation with early IL-1\u03b2 and IL-18 release and high caspase-1 activity, consistent with pyroptosis. In contrast, serotype II and especially hypervirulent serotype III isolates showed minimal early inflammasome activation but induced delayed immunoregulatory programs marked by elevated IL-10 and\n                      <jats:italic>ACOD1<\/jats:italic>\n                      expression. Reciprocal analyses revealed an inverse relationship between\n                      <jats:italic>ACOD1<\/jats:italic>\n                      and IL-1\u03b2 and a positive association between\n                      <jats:italic>ACOD1<\/jats:italic>\n                      and IL-10, indicating coordinated immunometabolic regulation. Serotype-specific glycolytic gene expression signatures appeared at later time points. Stratification by clinical metadata showed that isolates from preterm infants induced stronger early inflammatory responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study shows that GBS pathogenicity is not a uniform species-level trait but reflects isolate-specific abilities to reprogram macrophage immunity. By integrating temporal resolution with strain diversity, it provides a mechanistic framework linking macrophage immune trajectories to preterm birth\u2013associated inflammation and heterogeneous outcomes in neonatal infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1819218","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:25:07Z","timestamp":1776317107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Not all Group B Streptococci are alike: macrophage responses reveal inflammatory and immune-evasive strains"],"prefix":"10.3389","volume":"16","author":[{"given":"Larisa","family":"Jan\u017ei\u010d","sequence":"first","affiliation":[{"name":"Laboratory for Cellular Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucija","family":"Sr\u0161en","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Petrin","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alojz","family":"Ihan","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreja Nata\u0161a","family":"Kopitar","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.4103\/1673-5374.391330","article-title":"Metabolic reprogramming of the inflammatory response in the nervous system: the crossover between inflammation and metabolism","volume":"19","author":"Amo-Aparicio","year":"2024","journal-title":"Neural Regener. 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