Opposing signals from pathogen-associated molecular patterns and IL-10 are critical for optimal dendritic cell induction of in vivo humoral immunity to Streptococcus pneumoniae.
Interleukin10 is widely regarded as an inhibitor of immunity in part through its ability to inhibit dendritic cell (DC) function. The present study suggests a modification of this view by demonstrating instead that a critical balance exists between signals mediated by pathogen-associated molecular patterns and IL-10 for optimization of DC induction of an in vivo humoral immune response. Bone marrow-derived, CD8alpha(-) DC pulsed with Streptococcus pneumoniae in vitro induce in vivo protein- and polysaccharide-specific Ig isotype responses upon adoptive transfer into naive mice. Following bacterial activation, DC have a limited time during which they can function as effective APCs in vivo due to the onset of maturation-associated apoptosis. Autocrine IL-10, by limiting the time during which DC are responsive to widely varying levels of bacterial stimulation, delays the onset of DC apoptosis and thus prolongs the time during which DC are able to elicit in vivo humoral immunity. These data demonstrate a requirement for properly balanced positive and negative signaling in DC to optimize an in vivo immune response to a pathogen.
D000276:Adjuvants, Immunologic / Q000502:physiology; D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D017209:Apoptosis / Q000276:immunology; D019898:Autocrine Communication / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology* / Q000637:transplantation; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D006131:Growth Inhibitors / Q000502:physiology; D006358:Hot Temperature; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011135:Polysaccharides, Bacterial / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity*; D013997:Time Factors; D015164:Vaccines, Inactivated / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D006131:Growth Inhibitors; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011135:Polysaccharides, Bacterial; D015164:Vaccines, Inactivated; D016753:Interleukin-10; D018664:Interleukin-12