Early production of IL-22 but not IL-17 by peripheral blood mononuclear cells exposed to live Borrelia burgdorferi: the role of monocytes and interleukin-1.
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.
pharmazentrum frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt, Germany.
Malte
M
Bachmann
Katharina
K
Horn
Ina
I
Rudloff
Itamar
I
Goren
Martin
M
Holdener
Urs
U
Christen
Nicole
N
Darsow
Klaus-Peter
KP
Hunfeld
Ulrike
U
Koehl
Peter
P
Kind
Josef
J
Pfeilschifter
Peter
P
Kraiczy
Heiko
H
Mühl
D001706:Biopsy; D025065:Borrelia burgdorferi / Q000276:immunology*; D002478:Cells, Cultured; D015787:Erythema Chronicum Migrans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D000097043:Interleukin-22
D007375:Interleukin-1; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22