Borrelia burgdorferi Induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression.
The spirochete Borrelia burgdorferi is the agent of Lyme disease, which causes central nervous system manifestations in up to 20% of patients. We investigated the response of human brain microglial cells, glial progenitors, neurons, astrocytes, as well as peripheral blood monocytes to stimulation with B. burgdorferi. We used oligoarrays to detect changes in the expression of genes important for shaping adaptive and innate immune responses. We found that stimulation with B. burgdorferi lysate increased the expression of Toll-like receptors (TLRs) 1 and 2 in all cell types except neurons. However, despite similarities in global gene profiles of monocytes and microglia, only microglial cells responded to the stimulation with a robust increase in HLA-DR, HLA-DQ, and also coexpressed CD11-c, a dendritic cell marker. In contrast, a large number of HLA-related molecules were repressed at both the RNA and the protein levels in stimulated monocytes, whereas secretion of IL-10 and TNF-alpha was strongly induced. These results show that signaling through TLR1/2 in response to B. burgdorferi can elicit opposite immunoregulatory effects in blood and in brain immune cells, which could play a role in the different susceptibility of these compartments to infection.
Cassiani-Ingoni
Riccardo
R
Cellular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA. cassianr@ninds.nih.gov
Cabral
Erik S
ES
Lünemann
Jan D
JD
Garza
Zoila
Z
Magnus
Tim
T
Gelderblom
Harald
H
Munson
Peter J
PJ
Marques
Adriana
A
Martin
Roland
R
D025065:Borrelia burgdorferi / Q000502:physiology*; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005333:Fetus; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017628:Microglia / Q000378:metabolism* / Q000382:microbiology; D009000:Monocytes / Q000378:metabolism* / Q000382:microbiology; D009474:Neurons / Q000378:metabolism / Q000382:microbiology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2