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

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

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.

• Jezik: Angleški jezik
• Ključne besede: clinical isolate heterogeneity, Group B Streptococcus, immune evasion, inflammation, macrophages, preterm birth, pyroptosis
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 21 str.
• Številčenje: Vol. 16, art. 1819218
• PID: 20.500.12556/RUL-185398
• UDK: 616-097:577
• ISSN pri članku: 2235-2988
• DOI: 10.3389/fcimb.2026.1819218
• COBISS.SI-ID: 275427843
• Datum objave v RUL: 03.08.2026

Gradivo je del revije

• Naslov: Frontiers in cellular and infection microbiology
• Skrajšan naslov: Front. cell. infect. microbiol.
• Založnik: Frontiers Media
• ISSN: 2235-2988
• COBISS.SI-ID: 523093785

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: klinična heterogenost izolatov, streptokok skupine B, izogibanje imunskemu odzivu, vnetje, makrofagi, prezgodnji porod, piroptoza

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0083
• Naslov: Odnosi parazitskega obstajanja