IL-10 deficiency promotes increased Borrelia burgdorferi clearance predominantly through enhanced innate immune responses.
Borrelia burgdorferi is capable of persistently infecting a variety of hosts despite eliciting potent innate and adaptive immune responses. Preliminary studies indicated that IL-10-deficient (IL-10(-/-)) mice exhibit up to 10-fold greater clearance of B. burgdorferi from target tissues compared with wild-type mice, establishing IL-10 as the only cytokine currently known to have such a significant effect on spirochetal clearance. To further delineate these IL-10-mediated immune effects, kinetic studies indicated that spirochete dissemination to target tissues is similar in both wild-type and IL-10(-/-) mouse strains, and that enhanced clearance of B. burgdorferi in IL-10(-/-) mice is correlated with increased B. burgdorferi-specific Ab as early as 2 wk postinfection. Immunoblot analysis indicated that Abs produced by infected IL-10(-/-) and wild-type mice recognize similar ranges of spirochetal Ags. Immune sera from IL-10(-/-) and wild-type mice also exhibited similar bactericidal activity in vitro, and passive transfer of these immune sera into B. burgdorferi-infected SCID mice caused similar reductions of bacterial numbers in target tissues. Infectious dose studies indicated that 8-fold more B. burgdorferi were needed to efficiently infect naive IL-10(-/-) mice, suggesting these animals possess higher innate barriers to infection. Moreover, macrophages derived from IL-10(-/-) mice exhibit enhanced proinflammatory responses to B. burgdorferi stimulation compared with wild-type controls, and these responses are not significantly affected by the presence of immune serum. These findings confirm that B. burgdorferi clearance by innate immune responses is more efficient in the absence of IL-10, and these activities are not directly related to increased levels of B. burgdorferi-specific Ab.
Lazarus
John J
JJ
Department of Medical Microbiology and Immunology, Medical University of Ohio, Toledo, OH 43614, USA.
Meadows
Michelle J
MJ
Lintner
Robert E
RE
Wooten
R Mark
RM
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000916:Antibody Diversity / Q000235:genetics; D025065:Borrelia burgdorferi / Q000254:growth & development / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008826:Microbial Sensitivity Tests; D009895:Opsonin Proteins / Q000378:metabolism
D000907:Antibodies, Bacterial; D016207:Cytokines; D009895:Opsonin Proteins; D016753:Interleukin-10