Intrinsic Maturational Neonatal Immune Deficiencies and Susceptibility to Group B Streptococcus Infection

Korir, Michelle L.; Manning, Shannon D.; Davies, H. Dele

doi:10.1128/cmr.00019-17

Cited by 25 publications

(32 citation statements)

References 161 publications

(171 reference statements)

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“…One of the most well-studied virulence factors of GBS is its unique sialic acid-rich capsular polysaccharide (CPS) which inhibits complement deposition and protects the bacteria from opsonophagocytosis by immune cells, thus contributing to the evasion of host immune defense mechanisms. 30,31 The CPS also enhances biofilm formation, inhibits the binding of antimicrobial peptides and neutrophil extracellular traps (NET) as well as disturbing bacterial adherence to the epithelium and mucus, thus increasing GBS invasiveness. [32][33][34][35][36][37][38] GBS expresses 10 types of CPS (Ia, Ib, II-IX) that are structurally and antigenically different.…”

Section: Capsular Polysaccharide Conjugate Vaccinesmentioning

confidence: 99%

A Vaccine Against Group B Streptococcus: Recent Advances

Carreras-Abad¹,

Ramkhelawon²,

Heath³

et al. 2020

IDR

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Group B streptococcus (GBS) causes a high burden of neonatal and infant disease globally. Implementing a vaccine for pregnant women is a promising strategy to prevent neonatal and infant GBS disease and has been identified as a priority by the World Health Organisation (WHO). GBS serotype-specific polysaccharideprotein conjugate vaccines are at advanced stages of development, but a large number of participants would be required to undertake Phase III clinical efficacy trials. Efforts are therefore currently focused on establishing serocorrelates of protection in natural immunity studies as an alternative pathway for licensure of a GBS vaccine, followed by Phase IV studies to evaluate safety and effectiveness. Protein vaccines are in earlier stages of development but are highly promising as they might confer protection irrespective of serotype. Further epidemiological, immunological and health economic studies are required to enable the vaccine to reach its target population as soon as possible.

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Section: Capsular Polysaccharide Conjugate Vaccinesmentioning

confidence: 99%

A Vaccine Against Group B Streptococcus: Recent Advances

Carreras-Abad¹,

Ramkhelawon²,

Heath³

et al. 2020

IDR

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“…The role of on February 21, 2021 by guest http://iai.asm.org/ Downloaded from macrophages in responding to both neonatal and in utero infections is of particular relevance. Because neonates initially have an immature adaptive immune system, they rely heavily on the innate immune system, in which macrophages play a central role, to combat bacterial infections (5). Additionally, macrophages are one of the most prevalent immune system cells at the maternal-fetal interface, where they promote maternal tolerance to the developing fetus and destroy pathogens that have crossed the extraplacental membranes (6).…”

Section: Introductionmentioning

confidence: 99%

Distinct Group B Streptococcus Sequence and Capsule Types Differentially Impact Macrophage Stress and Inflammatory Signaling Responses

et al. 2021

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Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that can contribute to the induction of preterm birth in colonized pregnant women and to severe neonatal disease. Many questions regarding the mechanisms that drive GBS-associated pathogenesis remain unanswered, and it is not yet clear why virulence has been observed to vary so extensively across GBS strains. Previously, we demonstrated that GBS strains of different sequence types (STs) and capsule (CPS) types induce different cytokine profiles in infected THP-1 macrophage-like cells. Here, we have expanded on these studies by utilizing the same set of genetically diverse GBS isolates to assess ST and CPS-specific differences in upstream cell death and inflammatory signaling pathways. Our results demonstrate that particularly virulent STs and CPS types, such as the ST-17 and CPS III groups, induce enhanced JNK and NFκB pathway activation following GBS infection of macrophages when compared with other ST or CPS groups. Additionally, we found that ST-17, CPS III and CPS V GBS strains induce the greatest levels of macrophage cell death during infection and exhibit a more pronounced ability to be internalized and to survive in macrophages following phagocytosis. These data provide further support for the hypothesis that variable host innate immune responses to GBS, which significantly impact pathogenesis, stem in part from genotypic and phenotypic differences among GBS isolates. These and similar studies may inform the development of improved diagnostic, preventive, or therapeutic strategies targeting invasive GBS infections.

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“…Indeed, prior studies have shown that inappropriate inflammatory signaling can contribute to adverse pregnancy outcomes such as extraplacental membrane weakening and neonatal sepsis [3,4]. The macrophage response is of particular importance for neonates, whose immature adaptive immune system forces them to rely primarily on the innate immune system to combat bacterial infections [5]. Macrophages are also present at the maternal fetal interface where they aid in the maintenance of maternal tolerance to the developing fetus and combat pathogens that have crossed the extraplacental membranes [6].…”

Section: Introductionmentioning

confidence: 99%

Genetically distinct Group B Streptococcus strains induce varying macrophage cytokine responses

et al. 2019

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Group B Streptococcus (GBS) is an opportunistic pathogen that causes preterm birth and neonatal disease. Although GBS is known to exhibit vast diversity in virulence across strains, the mechanisms of GBS-associated pathogenesis are incompletely understood. We hypothesized that GBS strains of different genotypes would vary in their ability to elicit host inflammatory responses, and that strains associated with neonatal disease would induce different cytokine profiles than those associated with colonization. Using a multiplexed, antibody-based protein detection array, we found that production of a discrete number of inflammatory mediators by THP-1 macrophage-like cells was universally induced in response to challenge with each of five genetically distinct GBS isolates, while other responses appeared to be strain-specific. Key array responses were validated by ELISA using the initial five strains as well as ten additional strains with distinct genotypic and phenotypic characteristics. Interestingly, IL-6 was significantly elevated following infection with neonatal infection-associated sequence type (ST)-17 strains and among strains possessing capsule (cps) type III. Significant differences in production of IL1-β, IL-10 and MCP-2 were also identified across STs and cps types. These data support our hypothesis and suggest that unique host innate immune responses reflect strain-specific differences in virulence across GBS isolates. Such data might inform the development of improved diagnostic or prognostic strategies against invasive GBS infections.

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Intrinsic Maturational Neonatal Immune Deficiencies and Susceptibility to Group B Streptococcus Infection

Cited by 25 publications

References 161 publications

<p>A Vaccine Against Group B <em>Streptococcus</em>: Recent Advances</p>

<p>A Vaccine Against Group B <em>Streptococcus</em>: Recent Advances</p>

Distinct Group B Streptococcus Sequence and Capsule Types Differentially Impact Macrophage Stress and Inflammatory Signaling Responses

Genetically distinct Group B Streptococcus strains induce varying macrophage cytokine responses

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