Cobalt and Chromium Ions Impair Macrophage Response to <i>Staphylococcus aureus</i> Infection

Tölken, Lea A.; Wassilew, Georgi I.; Grolimund, Daniel; Weitkamp, Timm; Hesse, Bernhard; Rakow, Anastasia; Siemens, Nikolai; Schoon, Janosch

doi:10.1021/acsbiomaterials.3c01031

Cited by 1 publication

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References 67 publications

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“…The gating strategy to identify moDCs is shown in Additional file 1 : Figure S1. Macrophages were identified via CD68 and HLA-DR and monocytes via CD14 and CD16 staining as previously described [ 65 ]. Data were acquired using a FACSAria III flow cytometer and FACS DIVA 8.0 Software (both BD Biosciences, San Jose, CA, USA) and analyzed using FCS Express 7 Software (De Novo Software).…”

Section: Methodsmentioning

confidence: 99%

Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes

Tölken,

Paulikat,

Jachmann

et al. 2024

J Biomed Sci

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Background Streptococcus pyogenes (group A streptococcus, GAS) causes a variety of diseases ranging from mild superficial infections of the throat and skin to severe invasive infections, such as necrotizing soft tissue infections (NSTIs). Tissue passage of GAS often results in mutations within the genes encoding for control of virulence (Cov)R/S two component system leading to a hyper-virulent phenotype. Dendritic cells (DCs) are innate immune sentinels specialized in antigen uptake and subsequent T cell priming. This study aimed to analyze cytokine release by DCs and other cells of monocytic origin in response to wild-type and natural covR/S mutant infections. Methods Human primary monocyte-derived (mo)DCs were used. DC maturation and release of pro-inflammatory cytokines in response to infections with wild-type and covR/S mutants were assessed via flow cytometry. Global proteome changes were assessed via mass spectrometry. As a proof-of-principle, cytokine release by human primary monocytes and macrophages was determined. Results In vitro infections of moDCs and other monocytic cells with natural GAS covR/S mutants resulted in reduced secretion of IL-8 and IL-18 as compared to wild-type infections. In contrast, moDC maturation remained unaffected. Inhibition of caspase-8 restored secretion of both molecules. Knock-out of streptolysin O in GAS strain with unaffected CovR/S even further elevated the IL-18 secretion by moDCs. Of 67 fully sequenced NSTI GAS isolates, 28 harbored mutations resulting in dysfunctional CovR/S. However, analyses of plasma IL-8 and IL-18 levels did not correlate with presence or absence of such mutations. Conclusions Our data demonstrate that strains, which harbor covR/S mutations, interfere with IL-18 and IL-8 responses in monocytic cells by utilizing the caspase-8 axis. Future experiments aim to identify the underlying mechanism and consequences for NSTI patients.

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Section: Methodsmentioning

confidence: 99%