Possible role of glial cells in the onset and progression of Lyme neuroborreliosis.
BACKGROUND
Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.


METHODS
We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG).


RESULTS
ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis.


CONCLUSIONS
Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.
Ramesh
Geeta
G
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, LA, USA. gramesh@tulane.edu
Borda
Juan T
JT
Gill
Amy
A
Ribka
Erin P
EP
Morici
Lisa A
LA
Mottram
Peter
P
Martin
Dale S
DS
Jacobs
Mary B
MB
Didier
Peter J
PJ
Philipp
Mario T
MT
D000818:Animals; D000906:Antibodies / Q000097:blood; D017209:Apoptosis / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018925:Chemokines / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005911:Gliosis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D007964:Leukocytosis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D020852:Lyme Neuroborreliosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008253:Macaca mulatta; D008581:Meningitis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D009457:Neuroglia / Q000276:immunology* / Q000382:microbiology; D009474:Neurons / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011843:Radiculopathy / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*
D000906:Antibodies; D018925:Chemokines
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