Unknown

Dataset Information

0

Lipid-specific IgMs induce antiviral responses in the CNS: implications for progressive multifocal leukoencephalopathy in multiple sclerosis.


ABSTRACT: Progressive multi-focal leukoencephalopathy (PML) is a potentially fatal encephalitis caused by JC polyomavirus (JCV). PML principally affects people with a compromised immune system, such as patients with multiple sclerosis (MS) receiving treatment with natalizumab. However, intrathecal synthesis of lipid-reactive IgM in MS patients is associated with a markedly lower incidence of natalizumab-associated PML compared to those without this antibody repertoire. Here we demonstrate that a subset of lipid-reactive human and murine IgMs induce a functional anti-viral response that inhibits replication of encephalitic Alpha and Orthobunyaviruses in multi-cellular central nervous system cultures. These lipid-specific IgMs trigger microglia to produce IFN-? in a cGAS-STING-dependent manner, which induces an IFN-?/?-receptor 1-dependent antiviral response in glia and neurons. These data identify lipid-reactive IgM as a mediator of anti-viral activity in the nervous system and provide a rational explanation why intrathecal synthesis of lipid-reactive IgM correlates with a reduced incidence of iatrogenic PML in MS.

SUBMITTER: Hayden L 

PROVIDER: S-EPMC7427287 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Lipid-specific IgMs induce antiviral responses in the CNS: implications for progressive multifocal leukoencephalopathy in multiple sclerosis.

Hayden Lorna L   Semenoff Tiia T   Schultz Verena V   Merz Simon F SF   Chapple Katie J KJ   Rodriguez Moses M   Warrington Arthur E AE   Shi Xiaohong X   McKimmie Clive S CS   Edgar Julia M JM   Thümmler Katja K   Linington Chris C   Pingen Marieke M  

Acta neuropathologica communications 20200813 1


Progressive multi-focal leukoencephalopathy (PML) is a potentially fatal encephalitis caused by JC polyomavirus (JCV). PML principally affects people with a compromised immune system, such as patients with multiple sclerosis (MS) receiving treatment with natalizumab. However, intrathecal synthesis of lipid-reactive IgM in MS patients is associated with a markedly lower incidence of natalizumab-associated PML compared to those without this antibody repertoire. Here we demonstrate that a subset of  ...[more]

Similar Datasets

| S-EPMC5722774 | biostudies-literature
| S-EPMC3072716 | biostudies-literature
| S-EPMC8714204 | biostudies-literature
| S-EPMC4863751 | biostudies-other
| S-EPMC3256289 | biostudies-literature
| S-EPMC9291129 | biostudies-literature
| S-EPMC8739669 | biostudies-literature
| S-EPMC4465443 | biostudies-literature
| S-EPMC5172579 | biostudies-literature
| S-EPMC2919371 | biostudies-other