Cytokine IL-6 is required in Citrobacter rodentium infection-induced intestinal Th17 responses and promotes IL-22 expression in inflammatory bowel disease

Abstract

Citrobacter rodentium (C. rodentium) infection is a widely used murine model to mimic human enteric bacteria infection and inflammatory bowel disease (IBD). In this model, interleukin (IL)‑17A plays critical roles in increasing chemokine and cytokine production in various tissues to recruit innate cells, including monocytes and neutrophils, to the local site of infection. However, the source of IL‑17A remains unclear, as the majority of cell types produce IL‑17A, including intestinal endothelium cells, innate immune cells and CD4+ T cells in disease development. In the current study, wild‑type B6 mice were treated with C. rodentium and the CD4+ Th17 cell subset was observed as being specifically increased in Peyer's patches (PP), but not in mesenteric draining lymph nodes. Furthermore, the research suggested that the differentiation and activation of Th17 cells in PP were dependent on the inflammatory cytokine IL‑6, as blocking IL‑6 signaling with neutralizing antibodies decreased Th17 cells and resulted in the mice being more susceptible to C. rodentium infection. These results confirmed that the Th17 cell subset was specifically activated in PP and demonstrated that IL‑6 is required in Th17 cell activation, which are important to the clinical treatment of IBD.

Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia

“…Previous studies have shown that IL-6 is a pleiotropic cytokine involved in the cross talk between immune cells and stromal cells, activates the STAT3 signaling axis, is one of the main regulators of Th17 cell differentiation (46), and promotes IL-22 expression (24). IL-6-deficient mice showed an impaired defense against pneumococcal pneumonia (47).…”

Emerging Roles for Noncanonical NF-κB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology

“…The role of LTβR in IBD has been previously characterized in the Citrobacter rodentium infection model of IBD mucosal inflammation. C. rodentium infection results in epithelial hyperplasia and mild to moderate inflammation of the colonic mucosa that can be used as a murine model for some aspects of IBD (33). C. rodentium infection causes RORγt + cells to synthesize lymphotoxin (LT) which binds to LTβR on epithelial cells, resulting in the release of chemokines, such as CXCL-1 and CXCL-2, that recruit pro-inflammatory neutrophils and macrophages (34, 35).…”

Розвиток Імунної Відповіді При Стафілококовій Пневмонії (Частина 3)

“…Установ-лено, что возбуждение LTA и PGN Staphylococcus aureus рецептора TLR2 через MyD88/NF-κB сиг-нальный путь приводит к индукции синтеза IL-6 [60]. Взаимодействие SpA золотистого стафи-лококка с TNFR1 вызывает активацию фактора транскрипции NF-κB, а с EGFR -AP-1.…”

“…Интересно отметить, что при воспалении легких, вызванном PGN Staphylococcus aureus, вне зависимости от дозы IL-6 проявляет про-воспалительные свойства: способствует рекрутирова-нию полиморфноядерных лейкоцитов, формирова-нию абсцессов легочной ткани. У нокаутных мышей Il6 -/-активность воспалительной реакции легочной ткани не зависит от введенной дозы LTA, а характер воспаления отличается относительно низким уров-нем рекрутирования нейтрофилов [60].…”

“…Продемонстрировано, что после инкубации с LTA у макрофагов Il6 -/-наблюдается значительно более активная продукция TNF-α, чем у макрофа-гов Il6 +/+ [60]. По всей вероятности, данная зависи-мость продукции TNF-α обусловлена способностью IL-6 ингибировать транскрипцию гена TNF-α [91].…”