C5a Regulates NKT and NK Cell Functions in Sepsis
| Autor: | Jörg Köhl, Yves Laumonnier, Kasper Hoebe, Javid P. Mohammed, Jochen Mattner, Michael E. Fusakio |
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| Rok vydání: | 2011 |
| Předmět: |
Immunology
Complement C5a chemical and pharmacologic phenomena Cell Separation Complement receptor Biology Lymphocyte Activation Real-Time Polymerase Chain Reaction Article Flow cytometry Sepsis Mice Interleukin 21 medicine Animals Immunology and Allergy Receptor Receptor Anaphylatoxin C5a medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction hemic and immune systems Flow Cytometry medicine.disease Natural killer T cell Killer Cells Natural Mice Inbred C57BL Interleukin 12 Natural Killer T-Cells |
| Zdroj: | The Journal of Immunology. 187:5805-5812 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Complement, NKT, and NK cells play critical roles in the first line defense against pathogens. Functional roles for both C5a receptors, that is, complement receptor C5a (C5aR) and C5a receptor-like 2 (C5L2), in sepsis have been demonstrated. However, the role of C5a in innate lymphocyte activation during sepsis remains elusive. In this article, we show that naive NKT and NK cells already express high levels of C5aR and minor levels of C5L2 mRNA, but no protein. Upon Escherichia coli-induced sepsis, we found C5aR surface expression on subpopulations of NKT and NK cells, suggesting rapid translation into C5aR protein on bacterial encounter. Importantly, significantly increased survival in the absence of C5aR, NKT, and NK cells, but not of C5L2, was associated with reduced IFN-γ and TNF-α serum levels. Sepsis induction in C5aR+/C5aR− mixed bone marrow chimeras identified cognate engagement of C5aR on NKT cells as an important factor for the recruitment of NKT cells. Furthermore, we found synergistic interaction between C5aR and TLRs enhancing the production of TNF-α and IFN-γ from NKT and NK cells in cocultures with dendritic cells. Our results identify C5aR activation as a novel pathway driving detrimental effects of NKT and NK cells during early experimental sepsis. |
| Databáze: | OpenAIRE |
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