Ratio of T-Helper Type 1 (Th1) to Th17 Cytokines in Whole Blood Is Associated With Human β-Defensin 3 Expression in Skin and Persistent<i>Staphylococcus aureus</i>Nasal Carriage

Nurjadi, Dennis; Kain, Marlon; Marcinek, Patrick; Gaile, Marika; Heeg, Klaus; Zanger, Philipp

doi:10.1093/infdis/jiw440

Cited by 15 publications

(16 citation statements)

References 41 publications

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“…These were IL-4/IFN-␥ (indicator of Th2/Th1 balance) and IL-4/TNF-␣ (indicator of Th2 response/proinflammatory innate immune response). This approach has been extensively used in previous studies to determine the balance between anti-inflammatory and proinflammatory responses triggered by different stimuli (47)(48)(49). IL-4 was primarily considered as anti-inflammatory cytokine instead of IL-10 since IL-10 production is under the control of IL-4 (50-52).…”

Section: Methodsmentioning

confidence: 99%

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening

et al. 2020

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Cross-sectional studies conducted with obese and control subjects have suggested associations between gut microbiota alterations and obesity, but the links with specific disease phenotypes and proofs of causality are still scarce. The present study aimed to profile the gut microbiota of lean and obese children with and without insulin resistance to characterize associations with specific obesity-related complications and understand the role played in metabolic inflammation. Through massive sequencing of 16S rRNA gene amplicons and data analysis using a novel permutation approach, we have detected decreased incidence of Blautia species, especially Blautia luti and B. wexlerae, in the gut microbiota of obese children, which was even more pronounced in cases with both obesity and insulin resistance. There was also a parallel increase in proinflammatory cytokines and chemokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein 1 [MCP-1]) in feces of obese children compared to those of lean ones. B. luti and B. wexlerae were also shown to exert an anti-inflammatory effect in peripheral blood mononuclear cell cultures in vitro, compared to non-obesity-associated species. We suggest that the depletion of B. luti and B. wexlerae species in the gut ecosystem may occur in cases of obesity and contribute to metabolic inflammation leading to insulin resistance. IMPORTANCE Child obesity constitutes a risk factor for developing insulin resistance which, if sustained, could lead to more severe conditions like type 2 diabetes (T2D) in adulthood. Our study identified previously unknown species whose depletion (Blautia luti and Blautia wexlerae) is associated with insulin resistance in obese individuals. Our results also indicate that these bacterial species might help to reduce inflammation causally linked to obesity-related complications. Childhood is considered a window of opportunity to tackle obesity. These new findings provide, therefore, valuable information for the future design of microbiota-based strategies for the early prevention of obesity-related complications.

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Section: Methodsmentioning

confidence: 99%

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening

et al. 2020

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“…This was surprising and the authors suggested that IL-17 could be insoluble in nasal secretions ( Cole et al, 2016 ). Low Th1 to Th17 cytokines ratio were found to be predictive of S. aureus carriage in volunteers after whole blood stimulation with S. aureus ( Nurjadi et al, 2016 ). Future human studies should be conducted to better understand the role of Th17 cytokines in nasal carriage.…”

Section: Immune System and S Aureus Colonizationmentioning

confidence: 99%

Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections

et al. 2018

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Up to 30% of the human population are asymptomatically and permanently colonized with nasal Staphylococcus aureus. To successfully colonize human nares, S. aureus needs to establish solid interactions with human nasal epithelial cells and overcome host defense mechanisms. However, some factors like bacterial interactions in the human nose can influence S. aureus colonization and sometimes prevent colonization. On the other hand, certain host characteristics and environmental factors can predispose to colonization. Nasal colonization can cause opportunistic and sometimes life-threatening infections such as surgical site infections or other infections in non-surgical patients that increase morbidity, mortality as well as healthcare costs.

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“…Yet, a differential response to endogenous versus exogenous strains was observed, wherein individuals who carried a persistent strain responded to their endogenous strain with decreased IL-17, but not IFN-␥, levels. The lack of a differential IFN-␥ response is interesting, considering that Nurjadi et al found a significant difference in IFN-␥ mRNA expression between carriers and noncarriers (27). However, the model used by that group was looking at responses to one strain (essentially representing all strains) and not individual carried strains.…”

Section: Discussionmentioning

confidence: 99%

“…Nurjadi et al tested cytokine expression levels in persistent S. aureus carriers and noncarriers. They observed no difference in IL-17 mRNA expression between carriers and noncarriers but did observe a difference in gamma interferon (IFN-␥) expression between carriers and noncarriers and concluded that the ratio of IFN-␥ to IL-17 could be used to predict carriage (27).…”

mentioning

confidence: 99%

Staphylococcus aureus Colonization Induces Strain-Specific Suppression of Interleukin-17

et al. 2018

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is a pathogen that causes significant morbidity and mortality. Nasal carriage is a major source of transmission and of endogenous infection. Persistent carriage is detected in ∼30% of healthy individuals. While Th17 cells have been shown to play a role in infection and clearance, the immune response to carriage is not well understood. Here, we evaluate the Th17 response and its potential inhibitors during carriage. We recruited 25 volunteers, of whom 11 were persistent carriers. Volunteers' peripheral blood mononuclear cells (PBMCs) were stimulated with either their endogenous strain (a strain isolated from that carrier) or exogenous ones (strains not carried by that volunteer). Changes in Th17 cell frequency and numbers, interleukin-17 (IL-17) mRNA expression, and IL-17 protein abundance were measured by fluorescence-activated cell sorting, real-time PCR, and enzyme-linked immunosorbent assay. Similarly, responses of IL-17 suppressors (regulatory T cells [FOXP3], IL-10, IL-27, and IL-19) were measured. Th17 and IL-17 levels in response to stimulation with endogenous strains were significantly lower than those in response to stimulation with exogenous ones. Of the suppressive cytokines tested, only IL-19 exhibited a stronger response to endogenous than to exogenous strains. Addition of recombinant IL-19 to exogenous-strain-stimulated PBMCs caused decreased IL-17 expression, whereas addition of IL-19 antibodies to endogenous-strain-stimulated cells resulted in an increased IL-17 response. Together, our results suggest that carriage induced a tolerogenic response to a carried strain that could be reproduced through the addition of recombinant IL-19 or prevented by the addition of IL-19 antibodies. This differential immune response may play a role in the determination of carriage patterns.

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Ratio of T-Helper Type 1 (Th1) to Th17 Cytokines in Whole Blood Is Associated With Human β-Defensin 3 Expression in Skin and PersistentStaphylococcus aureusNasal Carriage

Abstract: A low Th1 to Th17 mRNA ratio increases the propensity for persistent S. aureus nasal colonization, with downregulated hBD-3 transcription providing a potential link.

Cited by 15 publications

References 41 publications

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening

Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections

Staphylococcus aureus Colonization Induces Strain-Specific Suppression of Interleukin-17

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