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

• Published in: Infection and immunity Vol. 86; no. 3
• Main Authors: Reiss-Mandel, Aylana, Rubin, Carmit, Zayoud, Morad, Rahav, Galia, Regev-Yochay, Gili
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.03.2018
• Subjects: Adult; Carrier State - immunology; Carrier State - microbiology; Female; Host Response and Inflammation; Humans; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukins - genetics; Interleukins - immunology; Leukocytes, Mononuclear - immunology; Male; Middle Aged; Nasal Mucosa - metabolism; Nasal Mucosa - microbiology; Species Specificity; Staphylococcal Infections - genetics; Staphylococcal Infections - immunology; Staphylococcal Infections - microbiology; Staphylococcus aureus - genetics; Staphylococcus aureus - growth & development; Staphylococcus aureus - physiology; Th17 Cells - immunology; Young Adult; carriage; IL-19; Staphylococcus aureus; IL-17
• ISSN: 0019-9567; 1098-5522; 1098-5522
• DOI: 10.1128/IAI.00834-17

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.