Coinfection with Borrelia burgdorferi and the agent of human granulocytic ehrlichiosis alters murine immune responses, pathogen burden, and severity of Lyme arthritis.
Lyme disease and human granulocytic ehrlichiosis (HGE) are tick-borne illnesses caused by Borrelia burgdorferi and the agent of HGE, respectively. We investigated the influence of dual infection with B. burgdorferi and the HGE agent on the course of murine Lyme arthritis and granulocytic ehrlichiosis. Coinfection resulted in increased levels of both pathogens and more severe Lyme arthritis compared with those in mice infected with B. burgdorferi alone. The increase in bacterial burden during dual infection was associated with enhanced acquisition of both organisms by larval ticks that were allowed to engorge upon infected mice. Coinfection also resulted in diminished interleukin-12 (IL-12), gamma interferon (IFN-gamma), and tumor necrosis factor alpha levels and elevated IL-6 levels in murine sera. During dual infection, IFN-gamma receptor expression on macrophages was also reduced, implying a decrease in phagocyte activation. These results suggest that coinfection of mice with B. burgdorferi and the HGE agent modulates host immune responses, resulting in increased bacterial burden, Lyme arthritis, and pathogen transmission to the vector.
Thomas
V
V
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Anguita
J
J
Barthold
S W
SW
Fikrig
E
E
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D023201:CD40 Ligand / Q000032:analysis; D016207:Cytokines / Q000097:blood; D004269:DNA, Bacterial / Q000032:analysis; D016873:Ehrlichiosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D008193:Lyme Disease / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009504:Neutrophils / Q000382:microbiology*; D013987:Ticks / Q000382:microbiology
D000907:Antibodies, Bacterial; D016207:Cytokines; D004269:DNA, Bacterial; D023201:CD40 Ligand