Adenosine deamination sustains dendritic cell activation in inflammation.
Adenosine is a suppressive agent that protects the host from excessive tissue injury associated with strong inflammation. In tissue stress, higher levels of adenosine signal through adenosine receptors to exert strong anti-inflammatory effects, and thus protect host cells. Existing evidence also suggests that elevated adenosine potently down-regulates the activation of lymphocytes during inflammation. This notion, however, is in contrast with another basic observation that the immune system is highly activated precisely under the same circumstances against pathogens. In this study, we show that inflammatory responses of dendritic cells (DCs) are highly sensitive to adenosine suppression. However, they intrinsically carry high adenosine deaminase activity, which in turn degrades and removes adenosine from the surroundings, cutting off DCs from the suppression. This regulatory mechanism is important in DC responses to pathogen-associated molecular patterns and their activation of T cells. Our findings suggest a mechanism that DCs maintain their hyperreactive state in inflammation despite the general state of suppression, and reveal a regulatory role of adenosine deaminase in DC innate immune responses.
Desrosiers
Melanie D
MD
Department of Microbiology and Infectious Diseases, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Cembrola
Katherine M
KM
Fakir
Michael J
MJ
Stephens
Leslie A
LA
Jama
Fatimina M
FM
Shameli
Afshin
A
Mehal
Wajahat Z
WZ
Santamaria
Pere
P
Shi
Yan
Y
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003641:Deamination; D003713:Dendritic Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D043682:Receptor, Adenosine A1 / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology
D058892:Adenosine Deaminase Inhibitors; D018836:Inflammation Mediators; D043682:Receptor, Adenosine A1; D051193:Toll-Like Receptors; D000243:Adenosine Deaminase; D000241:Adenosine