MECHANISMS OF CLEARANCE OF TREPONEMA-PALLIDUM FROM THE CSF IN A NONHUMAN PRIMATE MODEL

Objectives: To establish a model of CNS invasion by Treponema pallidum and to use it to investigate the immune mechanisms responsible for cl earance. Methods: Four macaques were intrathecally inoculated with 0.6 to 2.1 x 10(8) T. pallidum and underwent clinical examinations and bl ood and CSF collections every 1 to 2 weeks for 12 to 13 weeks. The fol lowing were determined: serum Venereal Disease Research Laboratory (VD RL) and microhemagglutination-T. pallidum reactivities, CSF-VDRL, CSF white blood cell (WBC) count, and the presence of viable T. pallidum i n CSF by the rabbit infectivity test (all animals), as well as the pre sence of T. pallidum in CSF by reverse-transcriptase (RT)-PCR, WBC phe notype by fluorescence-activated cell sorter, WBC cytokine production by RT-PCR, and brain MRI at 10 weeks (two animals). Results: All anima ls became systemically infected and developed CSF pleocytosis that res olved after 8 weeks. CSF T. pallidum was detected from 2 to 8 weeks. C SF T lymphocytes were predominantly CD4(+). Interferon-gamma (IFN-gamm a) mRNA was consistently detected in CSF WBCs, but interleukin (IL)-4 and IL-5 were not. AU animals remained clinically well. MRIs were norm al. Conclusions: In this model, T. pallidum is cleared from the CNS ju st as in most humans with early syphilis. Local production of IFN-gamm a likely participates in this process. This model could be used to cla rify the effect of retrovirus-induced immunodeficiency on clearance of T. pallidum from the CNS and on the local CNS immune response.