Borrelia burgdorferi infection regulates CD1 expression in human cells and tissues via IL1-β.
The appearance of group 1 CD1 proteins (CD1a, CD1b and CD1c) on maturing myeloid DC is a key event that converts myeloid DC to effective lipid APC. Here, we show that Borrelia burgdorferi, the causative agent of Lyme disease, triggers appearance of group 1 CD1 proteins at high density on the surface of human myeloid DC during infection. Within human skin, CD1b and CD1c expression was low or absent prior to infection, but increased significantly after experimental infections and in erythema migrans lesions from Lyme disease patients. The induction of CD1 was initiated by borrelial lipids acting through TLR-2 within minutes, but required 3 days for maximum effect. The delay in CD1 protein appearance involved a multi-step process whereby TLR-2 stimulated cells release soluble factors, which are sufficient to transfer the CD1-inducing effect in trans to other cells. Analysis of these soluble factors identified IL-1β as a previously unknown pathway leading to group 1 CD1 protein function. This study establishes that upregulation of group 1 CD1 proteins is an early event in B. burgdorferi infection and suggests a stepwise mechanism whereby bacterial cell walls, TLR activation and cytokine release cause DC precursors to express group 1 CD1 proteins.
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Konstantin
K
Yakimchuk
Carme
C
Roura-Mir
Kelly G
KG
Magalhaes
Annemieke
A
de Jong
Anne G
AG
Kasmar
Scott R
SR
Granter
Ralph
R
Budd
Allen
A
Steere
Victor
V
Pena-Cruz
Carsten
C
Kirschning
Tan-Yun
TY
Cheng
D Branch
DB
Moody
D018949:Antigens, CD1 / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D015787:Erythema Chronicum Migrans / Q000276:immunology; D006023:Glycoproteins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000378:metabolism*; D008055:Lipids / Q000276:immunology; D008193:Lyme Disease / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D015854:Up-Regulation
D018949:Antigens, CD1; C437944:CD1C protein, human; C419394:CD1b antigen; D006023:Glycoproteins; D053583:Interleukin-1beta; D008055:Lipids; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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