Murine Lyme disease: no evidence for active immune down-regulation in resolving or subclinical infection.
Macrophages in vitro rapidly ingest and kill Borrelia burgdorferi, yet some spirochetes in vivo may survive in the host and lead to complications of Lyme disease. One strategy for such survival may be the down-regulation of the immune system. To test this, we evaluated the degree of macrophage activation in a site of active disease-the heart-by examining cytokine expression in murine macrophages from control and B. burgdorferi-infected animals. Using double-label immunofluorescent staining in situ, we showed that infiltrating macrophages in infected hearts produce interleukin (IL)-1. By semiquantitative reverse transcription-polymerase chain reaction analysis, increased levels of mRNA were measured for the proinflammatory cytokines IL-1, tumor necrosis factor-alpha, and IL-12 during peak and resolving disease. No increases in the anti-inflammatory cytokines IL-10 and transforming growth factor-beta were detected. In an infected site without active disease--the peritoneal cavity--no increases in levels of proinflammatory or anti-inflammatory cytokines were detected in local macrophages. Thus, there is no evidence of pressure toward the down-regulation of inflammatory activity in the regions tested.
Montgomery
R R
RR
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA. ruth.montgomery@yale.edu
Wang
X M
XM
Malawista
S E
SE
D000818:Animals; D015748:Borrelia burgdorferi Group; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D007375:Interleukin-1 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009205:Myocarditis / Q000276:immunology*; D010537:Peritoneum / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12