title: Neurons are host cells for Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis infection of the central nervous system is thought to be initiated once the bacilli have breached the blood brain barrier and are phagocytosed, primarily by microglial cells. In this study, the interactions of M. tuberculosis with neurons in vitro and in vivo were investigated. The data obtained demonstrate that neurons can act as host cells for M. tuberculosis. M. tuberculosis bacilli were internalized by murine neuronal cultured cells in a time-dependent manner after exposure, with superior uptake by HT22 cells compared to Neuro-2a cells (17.7% versus 9.8%). Internalization of M. tuberculosis bacilli by human SK-N-SH cultured neurons suggested the clinical relevance of the findings. Moreover, primary murine hippocampus-derived neuronal cultures could similarly internalize M. tuberculosis. Internalized M. tuberculosis bacilli represented a productive infection with retention of bacterial viability and replicative potential, increasing 2- to 4-fold within 48 h. M. tuberculosis bacillus infection of neurons was confirmed in vivo in the brains of C57BL/6 mice after intracerebral challenge. This study, therefore, demonstrates neurons as potential new target cells for M. tuberculosis within the central nervous system.
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Sciences Faculty, University of Cape Town, Cape Town, South Africa.
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Randall
authors.forename: Nai-Jen
authors.initials: NJ
authors.lastname: Hsu
authors.forename: Dirk
authors.initials: D
authors.lastname: Lang
authors.forename: Susan
authors.initials: S
authors.lastname: Cooper
authors.forename: Boipelo
authors.initials: B
authors.lastname: Sebesho
authors.forename: Nasiema
authors.initials: N
authors.lastname: Allie
authors.forename: Roanne
authors.initials: R
authors.lastname: Keeton
authors.forename: Ngiambudulu M
authors.initials: NM
authors.lastname: Francisco
authors.forename: Sumayah
authors.initials: S
authors.lastname: Salie
authors.forename: Antoinette
authors.initials: A
authors.lastname: Labuschagné
authors.forename: Valerie
authors.initials: V
authors.lastname: Quesniaux
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Lauriston
authors.initials: L
authors.lastname: Kellaway
authors.forename: Muazzam
authors.initials: M
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D009474:Neurons / Q000382:microbiology*; D020306:Tuberculosis, Central Nervous System / Q000276:immunology / Q000382:microbiology*