If insufficiently treated, Lyme borreliosis can evolve into an inflammatory disorder affecting skin, joints, and the CNS. Early innate immunity may determine host responses targeting infection. Thus, we sought to characterize the immediate cytokine storm associated with exposure of PBMC to moderate levels of live Borrelia burgdorferi. Since Th17 cytokines are connected to host defense against extracellular bacteria, we focused on interleukin (IL)-17 and IL-22. Here, we report that, despite induction of inflammatory cytokines including IL-23, IL-17 remained barely detectable in response to B. burgdorferi. In contrast, T cell-dependent expression of IL-22 became evident within 10 h of exposure to the spirochetes. This dichotomy was unrelated to interferon-γ but to a large part dependent on caspase-1 and IL-1 bioactivity derived from monocytes. In fact, IL-1β as a single stimulus induced IL-22 but not IL-17. Neutrophils display antibacterial activity against B. burgdorferi, particularly when opsonized by antibodies. Since neutrophilic inflammation, indicative of IL-17 bioactivity, is scarcely observed in Erythema migrans, a manifestation of skin inflammation after infection, protective and antibacterial properties of IL-22 may close this gap and serve essential functions in the initial phase of spirochete infection.
Lyme borreliosis displays multifaceted clinical manifestations caused by the Borrelia burgdorferi sensu lato complex. If insufficiently treated, infection may proceed to inflammatory complications of chronic infection. Th17-like cytokines, foremost IL-17 and IL-22, are crucial for host defense against extracellular bacteria. IL-17/IL-22 secretion by human leukocytes exposed to live Borreliae has not been analyzed. Here we report that B. burgdorferi-activated PBMC lack immediate IL-17 expression despite being highly activated and robust T cell-dependent production of IL-22 that to a large part is mediated by monocyte-derived IL-1. Early innate immunity may shape dermal infection, thus likely affecting bacterial dissemination. Specifically, insufficient neutrophil recruitment/function, supposedly due to insufficient early IL-17 production along with a lack of opsonizing antibodies, may favor the spread of B. burgdorferi. Indeed, neutrophilic inflammation, indicative of IL-17 bioactivity, is scarcely observed in Erythema migrans, a manifestation of skin inflammation after infection. Production of IL-22 may fill this gap. Current knowledge on the role of IL-22 in epithelial biology in fact supports the hypothesis that IL-22 may serve as protection, particularly under conditions of inadequate neutrophil-driven host defense as seen early in B. burgdorferi infection.