The induction of inflammation by dectin-1 in vivo is dependent on myeloid cell programming and the progression of phagocytosis.
نویسندگان
چکیده
Dectin-1 is the archetypal signaling, non-Toll-like pattern recognition receptor that plays a protective role in immune defense to Candida albicans as the major leukocyte receptor for beta-glucans. Dectin-1-deficiency is associated with impaired recruitment of inflammatory leukocytes and inflammatory mediator production at the site of infection. In this study, we have used mice to define the mechanisms that regulate the dectin-1-mediated inflammatory responses. Myeloid cell activation by dectin-1 is controlled by inherent cellular programming, with distinct macrophage and dendritic cell populations responding differentially to the engagement of this receptor. The inflammatory response is further modulated by the progression of the phagocytosis, with "frustrated phagocytosis" resulting in dramatically augmented inflammatory responses. These studies demonstrate that dectin-1 in isolation is sufficient to drive a potent inflammatory response in a context-dependent manner. This has implications for the mechanism by which myeloid cells are activated during fungal infections and the processes involved in the therapeutic manipulation of the immune system via exogenous dectin-1 stimulation or blockade.
منابع مشابه
Phagocytosis Programming and the Progression of In Vivo Is Dependent on Myeloid Cell The Induction of Inflammation by Dectin-1
متن کامل
Internalization of Dectin-1 terminates induction of inflammatory responses
Dectin-1 is a pattern-recognition receptor recognizing beta-(1,3)-glucans found on fungal cell walls. Dectin-1 plays an important role in immunity to fungi by mediating phagocytic clearance of fungal particles and inducing transcription of innate response genes. We show here that the two processes are linked and that Dectin-1 signalling for inflammation is attenuated by phagocytosis. Blocking D...
متن کاملImpact of Ionizing Radiation on the Expression of CDC25A Phosphatase (in vivo)
Background and Objective: The cell division cycle 25 (CDC25)is a familyof highly conserved dual-specificity phosphatases that activate cyclin-dependent kinase complexes. These complexes are the main cell cycle regulators. Mammalian cells ,exposure to DNA damaging radiations such as ionizing radiation and ultraviolet light, prevent cell cycle progression by activation of checkpoint pathways an...
متن کاملInduction of Live Cell Phagocytosis by a Specific Combination of Inflammatory Stimuli
Conditions of severe hyper-inflammation can lead to uncontrolled activation of macrophages, and the ensuing phagocytosis of live cells. However, relationships between inflammatory stimuli and uncontrolled phagocytosis of live cells by macrophages are poorly understood. To identify mediators of this process, we established phagocytosis assays of live cells by stimulating macrophages with CpG DNA...
متن کاملMultiple Low Doses of 5-Fluorouracil Diminishes Immunosuppression by Myeloid Derived Suppressor Cells in Murine Melanoma Model
Background: Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cellsmediated immunosuppression. Objective: To assess whether multiple ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 181 5 شماره
صفحات -
تاریخ انتشار 2008