Borrelia burgdorferiStimulates the Production of Interleukin-10 in Peripheral Blood Mononuclear Cells from Uninfected Humans and Rhesus Monkeys

Abstract

Heat-killed Borrelia burgdorferi spirochetes stimulate in vitro production of interleukin-10 (IL-10) at both mRNA and protein levels in peripheral blood mononuclear cells (PBMC) of uninfected rhesus monkeys. A concomitant down-modulation of IL-2 gene transcription was observed. Neither IL-4 nor gamma interferon gene expression was ostensibly affected by B. burgdorferispirochetes. These phenomena were observed regardless of whether the stimulating spirochetes belonged to the B. burgdorferisensu stricto, Borrelia afzelii, or Borrelia garinii genospecies, the three main species that cause Lyme disease. B. burgdorferi also induced production of IL-10 in uninfected human PBMC, indicating that this effect might play a role in human Lyme disease. Purified lipidated outer surface protein A (OspA), but not its unlipidated form, induced the production of high levels of IL-10 in uninfected human PBMC. Thus, the lipid moiety is essential in the induction of IL-10 in these PBMC. B. burgdorferi M297, a mutant strain that lacks the plasmid that encodes OspA and OspB, also induced IL-10 gene transcription in PBMC, indicating that this phenomenon is not causally linked exclusively to OspA and its lipid moiety. These results demonstrate that B. burgdorferi can stimulate the production of an antiinflammatory, immunosuppressive cytokine in naive cells and suggest that IL-10 may play a role both in avoidance by the spirochete of deleterious immune responses and in limiting the inflammation that the spirochete is able to induce.

Differential acquired immune responsiveness to bacterial lipoproteins in Lyme disease‐resistant and ‐susceptible mouse strains

“…This inflammatory response thus requires prior exposure to B. burgdorferi. In contrast, peripheral blood mononuclear cells (PBMC) of naive rhesus macaques, or bone marrow macrophages of naive mice, are able to produce inflammatory cytokines, including IL-6, in response to lipoproteins or lipopeptides [14,30]. This apparent paradox may be explained in terms of the cellular composition of these cell compartments.…”

“…Mice (four to five per group) were subcutaneously inoculated in the cervical region with live lowpassage B. burgdorferi (4×10 6 spirochetes/mouse) of the JD1 strain. Spirochetes were cultivated as described previously [30].…”

The Pathogenesis of Lyme Neuroborreliosis: From Infection to Inflammation

“…It has been shown that B.b. induces the secretion of IL-10 in mononuclear cells (54), and the clearance of B.b. in IL-10 deficient mice is 10 times higher than in their wild-type littermates (55).…”

Pathogenesis of Lyme neuroborreliosis: Borrelia burgdorferi lipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes

“…We further hypothesized that the key B. burgdorferi effector molecules leading to reactive gliosis were lipoproteins. Spirochetal lipoproteins are potent immunopotentiators [21][22][23][24][25][26][27][28][29]. As many as 150 open reading frames potentially encoding lipoproteins have been identified in the genome of B. burgdorferi [30,31].…”