Complement C5a regulates IL-17 by affecting the crosstalk between DC and cd T cells in CLP-induced sepsis
نویسندگان
چکیده
Complement 5a (C5a) and Interleukin-17 (IL-17) are two important inflammatory mediators in sepsis. Here we studied the mechanisms underlying regulation of IL-17 by anaphylatoxin C5a. We found that C5a blockade increased the survival rate of mice following cecal ligation and puncture (CLP)-induced sepsis and decreased IL-17 expression in vivo. IL-17 was secreted mainly by cd T cells in this model. Importantly, our data suggest that C5a participates in the regulation of IL-17 secretion by cd T cells. Dendritic cells (DC) were found to act as a ‘‘bridge’’ between C5a and cd T cells in a mechanism involving IL-6 and transforming growth factor b (TGF-b). These results imply that C5a affects the crosstalk between DC and cd T cells during sepsis development, and this may result in a large production of inflammatory mediators such as IL-17.
منابع مشابه
C5a Regulates IL-12+DC Migration to Induce Pathogenic Th1 and Th17 Cells in Sepsis
OBJECTIVE It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs) to stimulate adaptive immune cells such as Th1 and Th17 in sepsis. METHODS Sepsis was induced by cecal ligation and puncture (CLP). CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+)DC, IFNγ(+)Th1, and IL-...
متن کاملNOD2-mediated Suppression of CD55 on Neutrophils Enhances C5a Generation During Polymicrobial Sepsis
Nucleotide-binding oligomerization domain (NOD) 2 is a cytosolic protein that plays a defensive role in bacterial infection by sensing peptidoglycans. C5a, which has harmful effects in sepsis, interacts with innate proteins. However, whether NOD2 regulates C5a generation during sepsis remains to be determined. To address this issue, cecal ligation & puncture (CLP)-induced sepsis was compared in...
متن کاملAnaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling
Activation of antigen-presenting dendritic cells (DCs) and the complement system are essential early events in the immune defense against invading pathogens. Recently, we and others demonstrated immunological crosstalk between signaling from receptors recognizing complement activation products and PAMPs on DCs. This affects DC effector function, as demonstrated by the finding that C5a prevents ...
متن کاملP183: Key Function of Complement System in Interactions between Pain and Nociceptors, C5a, and C3a
A part of the immune system that improves (complements) the ability of antibodies and phagocytic cells to clear microorganisms and injured cells from an organism, attacks the pathogen's cell membrane, and encourages inflammation called complement system. It is main part of immune system. Over thirty proteins and protein pieces compose the complement system, including cell membrane receptors, an...
متن کاملAn essential role for complement C5a in the pathogenesis of septic cardiac dysfunction
Defective cardiac function during sepsis has been referred to as "cardiomyopathy of sepsis." It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiom...
متن کامل