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

Abstract

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.

The Interleukin-10 Family of Cytokines and Their Role in the CNS

“…Gallagher et al ( 2000 ) described a list of potential IL-10 family members based upon homologous gene sequences. This work led to the identification of IL-19, a IL-10 homolog expressed by bacterial LPS challenged immune cells, including monocytes and T and B lymphocytes, which can be detected at sites such as the skin following Staphylococcus aureus infection (Gallagher et al, 2000 , 2004 ; Wolk et al, 2002 ; Reiss-Mandel et al, 2018 ).…”

IL-20 receptor cytokines in autoimmune diseases

“…IL-19 is considered to be a Th2 cytokine as it is not only produced by Th2 cells, but also exerts a positive feedback on Th2 cells for further Th2 cell differentiation and cytokine production, including IL-4, IL-5, IL-10 and IL-13 [25]. Reiss-Mandel et al demonstrated that IL-19 suppresses Staphylococcus aureus -induced IL-17A production from human peripheral blood mononuclear cells (PBMC) [26]; in line with this finding, Anuradha et al found that blocking IL-19 increases production of IFN-γ and IL-17A by CD4 + and CD8 + T cells in whole blood culture from filaria-infected individuals [27]. In contrast, Myles et al reported that Staphylococcus aureus infection in mice induces keratinocytes to produce IL-19, which significantly suppresses the production of IL-17A from γδ T cells [24].…”

Patterns and predictors ofStaphylococcus aureuscarriage during the first year of life; a longitudinal study

“…Previous findings by our group show that S. aureus carriers display a tolerogenic immune response to their own strain (25) and it is known that host-bacterial interactions in early life help shape the developing immune system and the commensal microbiome for years to come. These results, where we show that early acquisition of a strain predicts longer carriage during the first year of life, are consistent with the idea of a tolerogenic response to early acquisition of S. aureus , though long-term follow-up into late childhood or even adulthood are required to determine the implication of early S. aureus acquisition.…”