Monocyte‐mediated entry of pathogens into the central nervous system

Abstract

The origin of the microglia has long been a subject of debate. However it is now clear that monocytes enter the normal central nervous system and follow a series of morphological transformations as they differentiate into microglia. Thus, microglia are of monocytic origin. Since monocytes migrate into the normal CNS, they represent potential vehicles for the entry of pathogens into the nervous system and indeed may carry particulate matter into the CNS. Both viruses and bacteria use this 'Trojan horse' mechanism of entry in the pathogenesis of CNS disease.

Neuroinvasion of Fluorescein-Positive Monocytes in Acute Simian Immunodeficiency Virus Infection

“…Cells crossed the tight junctions at the vessel epithelium and basal lamina and exclusively localized to the perivascular space. In this study, SIV-infected cells and infiltrating monocytes colocalized to the perivascular regions in the cerebral cortex, further supporting the proposed role of monocytes in virus import into the CNS (25,51,60,62).…”

“…The SIV infection status of CFSE dye-labeled monocytes/macrophages in the CNS was not directly examined in this study, given the rarity of SIV RNA ϩ and CFSE dyelabeled cells along with limited tissue availability. Nevertheless, the SIV RNA ϩ cells and CFSE dye-labeled monocytes/macrophages localized to the same anatomical regions in the choroid plexus and cerebrum, consistent with the proposed role of monocytes as a "Trojan horse" for viral entry into the brain (25,51,60,62). …”

“…During infection with HIV and its simian counterpart SIV in the primate animal model for AIDS, monocytes constitute a principal virus reservoir (13,16,31) and are thought to disseminate the virus into the brain (25,51,60). HIV and SIV enter the central nervous system (CNS) early in acute infection (8,17,33,62), often resulting in the development of neurological complications and viral encephalitis late in the disease course with progression to AIDS (62).…”

Trojan Horse macrophages: studies with the murine lactate dehydrogenase-elevating virus and implications for sexually transmitted virus infection

“…injection, and demonstrate local penetration of macrophages from the vagina into placentas proximal to the cervix. Thus, internal spread of virus-infected macrophages would be expected to be highly efficient, in agreement with previous suggestions of 'Trojan Horse' virus-infected monocytes (Levy, 1988;Peluso et al, 1985;Ham et al, 1989;Williams & Blakemore, 1990). LDV-infected macrophages were also shown to function as infection delivery vehicles when injected into the vaginas of uninfected mice, and were capable of penetrating intact into the placenta, extending the Trojan Horse concept.…”

Meningoventriculitis Caused by Streptococcus pluranimalium in a Neonatal Calf of Premature Birth

“…Inflammatory lesions in the present calf extended from the ependyma to the deeper parenchyma in the upper segments of the spinal cord. In infections of neonates, macrophages carry bacteria to the meninges, choroid plexuses, and ventricular walls [1,13]. And the bactericidal capacity of macrophages of fetal animals has been shown to be lower than that of neonatal animals [6].…”