Early type I interferon response correlates with Borrelia burgdorferi dissemination in a mouse model of Lyme disease

Borrelia burgdorferi genotypes differ in their capacity to cause disseminated Lyme disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia genotypes in the blood of C3H mice during early dissemination following intradermal inoculation. The greatest responses were elicited by Borrelia turicatae , a relapsing fever spirochete that reaches high densities in the blood (313 entities; 170 induced, 143 repressed) and by B515, a B. burgdorferi clinical isolate that causes disseminated infection (129 entities; 52 induced, 77 repressed). Induced transcripts included IFN-responsive genes and genes involved in immunity and inflammation. B331, a B. burgdorferi clinical isolate that did not disseminate, stimulated changes in the fewest number of entities (1 induced, 4 repressed). Transcriptional regulation of type I IFN and IFN-related genes was measured by RT-PCR in mouse skin biopsies collected from the site of infection 24 hours after inoculation. The mean fold change values for Ifnb , Cxcl10 , Gbp1 , Ifit1 , Ifit3 , Irf7 , Mx1 , and Stat2 , were found to be significantly elevated in B515-infected mice relative to the control group. In contrast, transcription of these genes was not significantly changed in response to B331 or B31-4, a non-infectious B. burgdorferi mutant, although live B331 spirochetes could be recovered from skin. These results establish an association between B. burgdorferi genotype, dissemination, and early type I IFN induction.