Not all Group B Streptococci are alike : macrophage responses reveal inflammatory and immune-evasive strains

Janžič, Larisa (author), Sršen, Lucija (author), Petrin, Sara (author), Ihan, Alojz (author), Kopitar, Andreja Nataša (author)

Background: Group B Streptococcus (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. Methods: 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–associated 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. Results: 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-1β 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 ACOD1 expression. Reciprocal analyses revealed an inverse relationship between ACOD1 and IL-1β and a positive association between ACOD1 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. Conclusions: 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–associated inflammation and heterogeneous outcomes in neonatal infections.

• Language: English
• Keywords: clinical isolate heterogeneity, Group B Streptococcus, immune evasion, inflammation, macrophages, preterm birth, pyroptosis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 21 str.
• Numbering: Vol. 16, art. 1819218
• PID: 20.500.12556/RUL-185398
• UDC: 616-097:577
• ISSN on article: 2235-2988
• DOI: 10.3389/fcimb.2026.1819218
• COBISS.SI-ID: 275427843
• Publication date in RUL: 03.08.2026

Record is a part of a journal

• Title: Frontiers in cellular and infection microbiology
• Shortened title: Front. cell. infect. microbiol.
• Publisher: Frontiers Media
• ISSN: 2235-2988
• COBISS.SI-ID: 523093785

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: klinična heterogenost izolatov, streptokok skupine B, izogibanje imunskemu odzivu, vnetje, makrofagi, prezgodnji porod, piroptoza

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0083
• Name: Odnosi parazitskega obstajanja