The innate immune response to Salmonella enterica serovar Typhimurium by macrophages is dependent on TREM2-DAP12.
Macrophage recognition of Salmonella enterica serovar Typhimurium leads to a cascade of signaling events, including the activation of Src family and Syk kinases and the production of reactive oxygen species (ROS), which are critical for host innate defense during early stages of bacterial infection. ROS production depends on the NADPH oxidase, but little is known about the innate immune receptors and proximal adapters that regulate Salmonella-induced ROS. Herein, we demonstrate that serovar Typhimurium induces ROS through a pathway that requires both triggering receptor expressed on myeloid cells 2 (TREM2) and DAP12. This pathway is highly analogous to the pathways utilized by Fc receptors and integrins to regulate ROS production. Oral infection of mice with serovar Typhimurium demonstrates that the DAP12-dependent pathway regulates cecal colonization during early stages of Salmonella infection. Thus, DAP12 is an important regulator of Salmonella-induced ROS production in macrophages, and TREM2 is essential for linking DAP12 to the innate response to serovar Typhimurium.
Charles
Julia F
JF
Department of Medicine, University of California-San Francisco, San Francisco, California 94143, USA.
Humphrey
Mary Beth
MB
Zhao
Xiaodan
X
Quarles
Ellen
E
Nakamura
Mary C
MC
Aderem
Alan
A
Seaman
William E
WE
Smith
Kelly D
KD
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D002460:Cell Line; D005767:Gastrointestinal Diseases / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000502:physiology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse; C484963:Tyrobp protein, mouse