Protective role of IL-18 in host defenses against group B Streptococcus

Mancuso, Giuseppe; Midiri, Angelina; Beninati, Concetta; Zummo, Sebastiana; Biondo, Carmelo

doi:10.1007/s10096-021-04299-y

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…It is also worth noting that only infection with the non-virulent strain T15 induced transcriptional upregulation of the pro-inflammatory cytokine IL18. Studies in mice have suggested a protective role for IL-18 during group B Streptococcus infection [44]. Furthermore, it has been shown that IL-18 is necessary for the induction of streptococcal toxic shock-like syndrome during infection with the virulent serotype 2 S. suis strain SC-19 [45].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Host Responses to Infection with Streptococcus suis in a Porcine Precision-Cut Lung Slice Model: Between-Strain Differences Suggest Association with Virulence Potential

Weldearegay,

Brogaard,

Nerlich

et al. 2023

Pathogens

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Streptococcus suis is a porcine and zoonotic pathogen in the upper respiratory tract, expressing different capsular serotypes and virulence-associated factors. Given its genomic and phenotypic diversity, the virulence potential of S. suis cannot be attributed to a single factor. Since strong inflammatory response is a hallmark of S. suis infection, the objective of this study was to investigate the differences in transcriptional host responses to two serotype 2 and one serotype 9 strains. Both serotypes are frequently found in clinical isolates. We infected porcine precision-cut lung slices (PCLSs) with two serotype 2 strains of high (strain S10) and low (strain T15) virulence, and a serotype 9 strain 8067 of moderate virulence. We observed higher expression of inflammation-related genes during early infection with strains T15 and 8067, in contrast to infection with strain 10, whose expression peaked late. In addition, bacterial gene expression from infected PCLSs revealed differences, mainly of metabolism-related and certain virulence-associated bacterial genes amongst these strains. We conclude that the strain- and time-dependent induction of genes involved in innate immune response might reflect clinical outcomes of infection in vivo, implying rapid control of infection with less virulent strains compared to the highly virulent strain S10.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Host Responses to Infection with Streptococcus suis in a Porcine Precision-Cut Lung Slice Model: Between-Strain Differences Suggest Association with Virulence Potential

Weldearegay,

Brogaard,

Nerlich

et al. 2023

Pathogens

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“…IL-18 and IFN-γ are critical in human immunity and broadly protective against infection [48][49][50], therefore, they are commonly studied using primary human cells such as whole blood or PBMCs [6,[51][52][53][54]. Mice are frequently used to model infection, but only a few instances have il18 -/mice are susceptible to infection [19,[55][56][57]. This suggests that there could be differences in immune signaling between species.…”

Section: Il-18 Secretion Is Species-restrictedmentioning

confidence: 99%

Constitutive secretion of pro-IL-18 allows keratinocytes to initiate inflammation during bacterial infection

et al. 2023

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Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to pathogen invasion. Here, we characterized the proinflammatory cytokine repertoire produced by primary human keratinocytes and surrogate cell lines commonly used in vitro. Infection induces several cytokines and chemokines, but keratinocytes constitutively secrete IL-18 in a form that is inert (pro-IL-18) and lacks proinflammatory activity. Canonically, IL-18 activation and secretion are coupled through a single proteolytic event that is regulated intracellularly by the inflammasome protease caspase-1 in myeloid cells. The pool of extracellular pro-IL-18 generated by keratinocytes is poised to sense extracellular proteases. It is directly processed into a mature active form by SpeB, a secreted GAS protease that is a critical virulent factor during skin infection. This mechanism contributes to the proinflammatory response against GAS, resulting in T cell activation and the secretion of IFN-γ. Under these conditions, isolates of several other major bacterial pathogens and microbiota of the skin were found to not have significant IL-18-maturing ability. These results suggest keratinocyte-secreted IL-18 is a sentinel that sounds an early alarm that is highly sensitive to GAS, yet tolerant to non-invasive members of the microbiota.

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“…Nevertheless, IL-18 are IFN-γ and critical in human immunity and are protective against infection [44][45][46]. Only a few instances have been identified where il18 -/mice are susceptible to infection [19,[47][48][49], suggesting differences in immune signaling between species or methods for modeling infection fail to capture IL-18-mediated signaling. IL-18 and T cell responses are instead commonly approached using human primary cells such whole blood or PBMCs to get around limitations imposed by mice [43,[50][51][52][53].…”

Section: Speb-activated Il-18 Induces Inflammationmentioning

confidence: 99%

Pro-IL-18 secreted by keratinocytes detects the group A streptococcal protease SpeB

Johnson

Sands

Trivedi

et al. 2021

Preprint

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Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to pathogen invasion. Here, we characterized the proinflammatory cytokine repertoire produced by primary human keratinocytes and surrogate cell lines commonly used in vitro. Infection induces several cytokines and chemokines, but keratinocytes constitutively secrete IL-18 in a form that is inert (pro-IL-18) and lacks proinflammatory activity. Canonically, IL-18 activation and secretion are coupled through a single proteolytic event that is regulated intracellularly by the inflammasome protease caspase-1 in myeloid cells. The pool of extracellular pro-IL-18 generated by keratinocytes is poised to sense extracellular proteases and is directly processed into a mature active form by SpeB, a secreted GAS protease that is a critical virulent factor during skin infection. This mechanism contributes to the proinflammatory response against GAS, resulting in T cell activation and the secretion of IFN-γ that restrict GAS growth. Other major bacterial pathogens and microbiota of this skin did not have significant IL-18-maturing ability. Taken together, these results suggest keratinocyte-secreted IL-18 is a sentinel that sounds an early alarm that is highly sensitive to GAS, yet tolerant to non-invasive members of the microbiota.

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Protective role of IL-18 in host defenses against group B Streptococcus

Cited by 4 publications

References 24 publications

Transcriptional Host Responses to Infection with Streptococcus suis in a Porcine Precision-Cut Lung Slice Model: Between-Strain Differences Suggest Association with Virulence Potential

Transcriptional Host Responses to Infection with Streptococcus suis in a Porcine Precision-Cut Lung Slice Model: Between-Strain Differences Suggest Association with Virulence Potential

Constitutive secretion of pro-IL-18 allows keratinocytes to initiate inflammation during bacterial infection

Pro-IL-18 secreted by keratinocytes detects the group A streptococcal protease SpeB

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