<b><i>Staphylococcus aureus</i></b> Induces Shedding of IL-1RII in Monocytes and Neutrophils

Abstract

Interleukin 1 (IL-1) β is a critical cytokine that orchestrates host defenses against Staphylococcus aureus and is crucial for the eradication of bacteria. The production and action of IL-1β are regulated by multiple control pathways. Among them, IL-1RII (the type II IL-1 receptor) acts as a decoy receptor and has been shown to regulate the biological effects of IL-1β. High levels of soluble IL-1RII are present in septic patients; however, the stimuli that regulate the expression and release of IL-1RII in pathological conditions are incompletely elucidated. In the present study, we demonstrated the ability of S. aureus and protein A to induce IL-1RII shedding in myeloid cells. The positive modulation of IL-1RII expression and cleavage was associated with the failure to detect IL-1β in response to S. aureus both in vitro and in vivo, suggesting that the soluble form of the receptor could be masking the availability of IL-1β. The absence of detectable IL-1β was associated with low levels of inflammatory cytokines and chemokines known to be regulated by IL-1β and with increased bacterial persistence. Modulation of decoy receptors during systemic S. aureus infection is proposed as a new strategy used by this bacterium to evade the immune response.

Identification and Characterization of Staphylococcus aureus Strains with an Incomplete Hemolytic Phenotype

“…During the infection process of invasive S. aureus , pathogen-associated-molecules initiate the innate immune system leading to activation and recruitment of neutrophils and macrophages and the production of pro-inflammatory cytokines, most notably TNF-α, IL-1β, and IL-6 (Bekeredjian-Ding et al, 2015; Giai et al, 2016; Zhao et al, 2016). It was reported that the secretion of inflammatory cytokines IL-6 increased with increasing concentrations of S. aureus (Chen et al, 2016).…”

Tuning inflammation and immunity by the negative regulators IL‐1R2 and IL‐1R8

“…Recently, it was shown that Staphylococcus aureus induces IL‐1R2 shedding by myeloid cells and that in monocytes the release of IL‐1R2 was highly dependent on the expression of protein A, a complex virulence factor, contributing to evasion of immune clearance. S. aureus protein A rapidly activated ADAM17 in airway epithelial cells and macrophages, leading to IL‐1R2 shedding and consequently reducing IL‐1β availability, therefore negatively modulating the subsequent inflammatory response critical for bacterial eradication during early systemic infection and contributing to the bacterial persistence in blood . Thus, IL‐1R2 shedding by S. aureus would represent a novel mechanism of immune evasion by this microorganism.…”

“…S. aureus protein A rapidly activated ADAM17 in airway epithelial cells and macrophages, leading to IL-1R2 shedding and consequently reducing IL-1β availability, therefore negatively modulating the subsequent inflammatory response critical for bacterial eradication during early systemic infection and contributing to the bacterial persistence in blood. 61 Thus, IL-1R2 shedding by S. aureus would represent a novel mechanism of immune evasion by this microorganism.…”

<b><i>Journal of Innate Immunity</i></b> Ten Years Later

“…It is, by some measures, the most important type of immunity we have.” has lost none of its actuality. From the beginning, the journal has been covering research in the area of innate immunity in a broad sense, for example invertebrate immunity [4-6], innate recognition [7-9], the cell biology of innate immune cells [10-12], and complex human diseases [13-15]. …”