title: Increasing the recruitment of neutrophils to the site of infection dramatically attenuates Borrelia burgdorferi infectivity.
abstract: Borrelia burgdorferi infection causes an initial skin lesion called erythema migrans (EM) in human Lyme disease and in models of monkey and rabbit borreliosis. EM results from the inflammatory response triggered by spirochete replication and likely develops to contain the initial infection but allows bacterial dissemination to occur. The essential lack of neutrophil involvement in EM histopathology prompted us to examine the consequence of increasing their recruitment in the inflammatory response to the Lyme disease agent. B. burgdorferi was modified genetically to constitutively express and secrete the chemokine KC, a neutrophil chemoattractant. After inoculation into the dermis of the murine host, control spirochetes induced an infiltration of macrophages, neutrophils, and basophils within 6 h; however, the recruited neutrophils and basophils were quickly substituted by eosinophils, and the inflammatory response became macrophage dominant by 16 h. Such a response failed to contain the initial infection and allowed the spirochetes to disseminate. In contrast, B. burgdorferi with KC secretion induced an intensive neutrophil infiltration at the inoculation site, and as a result, the host's ability to control the initial infection was greatly enhanced. Taken together, this study suggests that the failure of sufficient neutrophil recruitment and activation during the initial inflammatory response may allow B. burgdorferi to effectively colonize the mammalian host.
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Xu
authors.forename: Sunita V
authors.initials: SV
authors.lastname: Seemanapalli
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Reif
authors.forename: Charles R
authors.initials: CR
authors.lastname: Brown
authors.forename: Fang Ting
authors.initials: FT
authors.lastname: Liang
mesh_terms: D000818:Animals; D025065:Borrelia burgdorferi / Q000276:immunology / Q000472:pathogenicity; D002465:Cell Movement; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000502:physiology; D008193:Lyme Disease / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D010587:Phagocytosis; D051381:Rats
chemical_list: D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse