MyD88 deficiency enhances acquisition and transmission of Borrelia burgdorferi by Ixodes scapularis ticks.
Borrelia burgdorferi strains exhibit various degrees of infectivity and pathogenicity in mammals, which may be due to their relative ability to evade initial host immunity. Innate immune cells recognize B. burgdorferi by Toll-like receptors (TLRs) that use the intracellular molecule MyD88 to mediate effector functions. To determine whether impaired TLR signaling enhances Ixodes scapularis acquisition of B. burgdorferi, we fed nymphs on wild-type (WT) and MyD88-/- mice previously infected with two clinical isolates of B. burgdorferi, BL206, a high-virulence strain, and B348, an attenuated strain. Seventy-three percent of the nymphs that fed on BL206-infected WT mice and 40% of the nymphs that fed on B348-infected WT mice acquired B. burgdorferi, whereas 100% of the nymphs that fed on MyD88-/- mice became infected, irrespective of B. burgdorferi strain. Ticks that acquired infection after feeding on MyD88-/- mice harbored more spirochetes than those that fed on WT mice, as assessed by quantitative PCR for B. burgdorferi DNA. Vector transmission of BL206 and B348 was also enhanced when MyD88-/- mice were the blood meal hosts, with the mean pathogen burden at the skin inoculation site significantly higher than levels in WT mice. These results show that the absence of MyD88 facilitates passage of both low- and high-infectivity B. burgdorferi strains between the tick vector and the mammal and enhances the infectivity of a low-infectivity B. burgdorferi strain.
Bockenstedt
Linda K
LK
S-525C TAC, Section of Rheumatology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8031, USA. linda.bockenstedt@yale.edu
Liu
Nengyin
N
Schwartz
Ira
I
Fish
Durland
D
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001096:Arachnid Vectors / Q000276:immunology / Q000382:microbiology; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D025065:Borrelia burgdorferi / Q000276:immunology*; D005247:Feeding Behavior / Q000502:physiology; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D018884:Ixodes / Q000276:immunology / Q000382:microbiology*; D008193:Lyme Disease / Q000235:genetics / Q000469:parasitology* / Q000635:transmission*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D013984:Tick Infestations / Q000276:immunology / Q000382:microbiology
D048868:Adaptor Proteins, Signal Transducing; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88