Search

• C. perfringens triggers classical phagocyte ETs formation. • Bacteria induce ETs release via ERK1/2-, P38 MAPK- and SOCE-dependent mechanisms. • A beneficial role of phagocyte ETs on pathogen control in vitro and in vivo. Clostridium perfringens (C. perfringens) is an important Gram-positive anaerobic spore-forming pathogen that provokes life-threatening gas gangrene and acute enterotoxaemia, although it colonizes as a component of the symbiotic bacteria in humans and animals. However, the mechanisms by which C. perfringens is cleared from the host remains poorly understood, thereby impeding the development of novel strategies for control this infection. Here, we uncover a beneficial effect of extracellular traps (ETs) formation on bacterial killing and clearance by phagocytes. C. perfringens strain ATCC13124, and wild-type isolates CP1 and CP3 markedly trigger ETs formation in macrophages and neutrophils. As expected, visualization of DNA decorated with histone, myeloperoxidase (MPO) and neutrophils elastase (NE) in C. perfringens -triggered classical ETs structures. Notably, the bacteria-induced ETs formation is an ERK1/2-, P38 MAPK-, store-operated calcium entry (SOCE)-, NADPH oxidase-, histone-, NE-, and MPO-dependent process, and is independent of LDH activity. Meanwhile, the defect of bactericidal activity is mediated by impairing ETs formation in phagocytes. Moreover, In vivo studies indicated that degradation of ETs by DNase I administration leads to a defect in the protection against experimental gas gangrene, with higher mortality rates, exacerbated tissue damage, and more bacterial colonization. Together, these results suggest that phagocyte ETs formation is essential for the host defense against C. perfringens infection. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4+ CD25+ Foxp3+ regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE−/− mice. Methods and results: Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE−/− mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE−/− mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (RORγt) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-β1) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8–16weeks of age) in ApoE−/− mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE−/− mice than in their age-matched wild-type littermates. Conclusions: Th17/Treg functional imbalance exists during atherogenesis in ApoE−/− mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis. [Copyright &y& Elsevier]