Innate instruction of CD4+ T cell immunity in respiratory bacterial infection.
The innate immune system recognizes invading microbes via conserved pattern recognition receptors and uses inflammatory signals to concert adaptive defense mechanisms. However, microbial and host parameters involved in CD4 T cell priming and direction of Th1, Th2, and Th17 differentiation in the context of infections with complex pathogens in vivo are incompletely understood. In this study, we used Legionella pneumophila, which triggers membrane-bound and cytosolic pattern recognition receptors, to study the innate instruction of adaptive immunity. Upon airway infection, T cells were primed exclusively in the lung-draining lymph nodes and differentiated into Th1/Th17 effector cells upon arrival in the lung. Although engagement of membrane-bound pattern recognition receptors was sufficient for initial T cell activation and proliferation, cytosolic pattern recognition was required for effector T cell differentiation. In the absence of cytoplasmic pattern recognition, MyD88 was key for T cell priming, whereas, in its presence, MyD88-mediated signals were crucial for Th17 differentiation. Specifically, cytosolic sensing of Legionella-derived flagellin, inflammasome activation, and IL-1 signaling contributed to Th17 development. In the absence of TLR signaling, a simultaneous Th1/Th2 response developed that was independent of the inflammasome-IL-1 axis. Collectively, these data illustrate the important role for various pattern recognition receptors triggered by complex pathogens and how they each instruct specific differentiation programs in responding CD4 T cells.
Institute of Microbiology, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
Gerhard
G
Trunk
Annette
A
Oxenius
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000276:immunology; D007113:Immunity, Innate; D016952:Legionella pneumophila / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014774:Virulence / Q000276:immunology
D001426:Bacterial Proteins