Central and peripheral nervous system infection, immunity, and inflammation in the nonhuman primate model of lyme borreliosis

Abstract

The relationship between chronic infection, antispirochetal immunity, and inflammation is unknown in Lyme neuroborreliosis. In the nonhuman primate model of Lyme neuroborreliosis, we measured spirochetal density in the nervous system and other tissues by polymerase chain reaction and correlated these values to anti-Borrelia burgdorferi antibody in the serum and cerebrospinal fluid, and to inflammation in tissues. Despite substantial presence of Borrelia burgdorferi, the causative agent of Lyme borreliosis, in the central nervous system, only minor inflammation was present there, though skeletal and cardiac muscle, which contained similar levels of spirochete, were highly inflamed. Anti-Borrelia burgdoferi antibody was present in the cerebrospinal fluid but was not selectively concentrated. All infected animals developed anti-Borrelia burgdorferi antibody in the serum, but increased amplitude of antibody was not predictive of higher levels of infection. These data demonstrate that Lyme neuroborreliosis is a persistent infection, that spirochetal presence is a necessary but not sufficient condition for inflammation, and that antibody measured in serum may not predict the severity of infection.

The mammalian host response to borrelia infection

“…Two to four months after intradermal inoculation by syringe we found N40 DNA by PCR in all the tissues examined in both immunocompetent and immunosuppressed animals [1,4,5,8,14,15]. However, the [8].…”

“…For this we did microscopical examination of H&E-and immunostained tissue sections and measured mRNA and protein by RT-PCR and immuno-dot-blot, respectively [1,4,5,8,[14][15][16]18]. First we studied the presence and severity of inflammation in tissues from immunocompetent and immunosuppressed non-human primates inoculated with the N40 strain of B. burgdorferi [8].…”

Relation entre lombosciatique, hernie discale et neuroborréliose : à propos de quatre observations

“…Les anomalies électrophysiologiques, témoi-gnant le plus souvent d'une atteinte axonale, régressent fré-quemment parallèlement à l'évolution clinique [6,23]. Une étude récente sur modèle de primates montre que la neuroborréliose est une infection persistante et que la présence de la bactérie est une condition nécessaire mais non suffisante pour générer une inflammation [27]. Une étude sur 103 patients souffrant de lomboradiculalgies a permis de retrouver chez trois d'entre eux la coexistence d'une hernie discale avec une synthèse intrathécale d'anticorps spécifiques de B. burgdorferi, mais les auteurs écartent la possibilité d'une origine infectieuse en raison de l'absence de radiculite aiguë et de réaction cellulaire associée [28].…”

Counterpoint: Long-Term Antibiotic Therapy Improves Persistent Symptoms Associated with Lyme Disease

“…Finally, in a model using our closest relative, the nonhuman primate macaque monkey, Pachner and colleagues [71][72][73][74][75] found that neurologic and cardiac disease were associated with persistent infection in these monkeys, and cytokine and gene expression related to persistent B. burgdorferi infection could be demonstrated 13 months after infection. In summary, these animal models provide "credible scientific evidence" for persistent infection in Lyme disease.…”

“…We can start with animal models of Lyme disease [67][68][69][70][71][72][73][74][75]. In the mouse, one study found that "persistence of spirochetes within macrophages provides a possible pathogenetic mechanism for chronic or recurring Lyme disease" [67, p. 909].…”