Bacteria and their cell wall components uniformly co-activate interleukin-17-producing thymocytes

Abstract

SummaryInterleukin (IL)-17-producing T cells play a critical role in the immune response against microbial pathogens. Traditionally, experimental studies have focused upon understanding the activity of IL-17-producing T cells which differentiate from naive T cells in the peripheral immune system. However, we have demonstrated previously that IL-17-producing T cells are also present in the thymus of naive wild-type mice and can be co-activated there by microbial stimuli. Other studies have supported the concept that IL-17-producing thymocytes have a specific role in the immediate defence against microbial pathogens, which is independent from the development of an adaptive immune response. Given an important role of the thymus in systemic bacterial infection and sepsis, in this study we investigate the effect of a broad spectrum of bacteria and cell wall components on thymocyte cytokine production. Surprisingly, we find that all types of bacteria investigated (including non-pathogenic species) uniformly activate IL-17-producing thymocytes upon α-CD3 stimulation. In contrast, there is a heterogeneous effect on IL-6 and interferon (IFN)-γ-production with Gram-negative bacteria inducing far higher frequencies of IL-6-and IFN-γ-producing thymocytes than Gram-positive bacteria. We conclude that IL-17-producing thymocytes constitute a 'first line of recognition', but not a 'first line of defence' against bacteria in general. Their activity might lead to immune activation, but not necessarily to a pathological inflammatory disease condition. The difference between these two states might be determined by other immunological effector molecules, such as IL-6 and IFN-γ.

Pseudomonas aeruginosa and Its Bacterial Components Influence the Cytokine Response in Thymocytes and Splenocytes

“…HKPA is recognized by the immune system via TLR2, whereas LPS is recognized via TLR4. This means that the cytokine response to bacteria is not only mediated through TLR2 activation but also that cell wall components are able to activate other pathways that trigger the cytokine secretion of immature and mature immune cells, which correlates with our previous studies (2,5,27,31,32). We found that LPS is responsible for the activation of the Notch2 ϩ signaling of mature immune cells.…”

“…N-Acyl-homoserine lactones from P. aeruginosa are signaling molecules produced inside the cell and involved in bacterial quorum sensing to regulate gene expression (26). We have previously demonstrated that bacteria and their cell wall components influence the cytokine response of thymocytes (27). These are recognized predominantly by Toll-like receptor 2 (TLR2).…”

Relationship between physical activity, healthy lifestyle and COVID-19 disease severity; a cross-sectional study

“…In fact, studies suggest that some dietary patterns may affect inflammatory markers linked to low-grade systemic inflammation (Casas et al 2014 ; Del Chierico et al 2014 ). Generally, low-grade inflammation appears to be associated with IL-17 and IL-10 ratios while IL-17 plays an important role in host defense against infections by absorbing neutrophils and producing antimicrobial peptides (Weber et al 2014 ).…”

Childhood Obesity: Immune Response and Nutritional Approaches

“…IL-17 has been associated to the pathogenesis of multiple autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel diseases ( 47 ). IL-17 also plays a crucial role in host defense upon bacterial and fungal infections by recruiting neutrophils and producing antimicrobial peptides (AMPs) ( 48 ). Th17 cells release multiple molecules of IL-17 (A–F) ( 49 ) and IL-17F was also found to be co-expressed in Th17 cells, thus contributing to host defenses, inflammatory, allergic, and autoimmune functions of Th17 cells ( 50 ).…”