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Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus.

Publication ,  Journal Article
Iannacone, M; Moseman, EA; Tonti, E; Bosurgi, L; Junt, T; Henrickson, SE; Whelan, SP; Guidotti, LG; von Andrian, UH
Published in: Nature
June 24, 2010

Lymph nodes (LNs) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. Recent work has shown that CD11b(+)CD169(+) macrophages, which populate the subcapsular sinus (SCS) of LNs, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses. Here we show, using vesicular stomatitis virus (VSV), a relative of rabies virus transmitted by insect bites, that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS). On local depletion of LN macrophages, about 60% of mice developed ascending paralysis and died 7-10 days after subcutaneous infection with a small dose of VSV, whereas macrophage-sufficient animals remained asymptomatic and cleared the virus. VSV gained access to the nervous system through peripheral nerves in macrophage-depleted LNs. In contrast, within macrophage-sufficient LNs VSV replicated preferentially in SCS macrophages but not in adjacent nerves. Removal of SCS macrophages did not compromise adaptive immune responses against VSV, but decreased type I interferon (IFN-I) production within infected LNs. VSV-infected macrophages recruited IFN-I-producing plasmacytoid dendritic cells to the SCS and in addition were a major source of IFN-I themselves. Experiments in bone marrow chimaeric mice revealed that IFN-I must act on both haematopoietic and stromal compartments, including the intranodal nerves, to prevent lethal infection with VSV. These results identify SCS macrophages as crucial gatekeepers to the CNS that prevent fatal viral invasion of the nervous system on peripheral infection.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

June 24, 2010

Volume

465

Issue

7301

Start / End Page

1079 / 1083

Location

England

Related Subject Headings

  • Vesiculovirus
  • Vesicular stomatitis New Jersey virus
  • Vesicular stomatitis Indiana virus
  • Survival Rate
  • Rhabdoviridae Infections
  • Receptor, Interferon alpha-beta
  • Peripheral Nerves
  • Paralysis
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
 

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Iannacone, M., Moseman, E. A., Tonti, E., Bosurgi, L., Junt, T., Henrickson, S. E., … von Andrian, U. H. (2010). Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature, 465(7301), 1079–1083. https://doi.org/10.1038/nature09118
Iannacone, Matteo, E Ashley Moseman, Elena Tonti, Lidia Bosurgi, Tobias Junt, Sarah E. Henrickson, Sean P. Whelan, Luca G. Guidotti, and Ulrich H. von Andrian. “Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus.Nature 465, no. 7301 (June 24, 2010): 1079–83. https://doi.org/10.1038/nature09118.
Iannacone M, Moseman EA, Tonti E, Bosurgi L, Junt T, Henrickson SE, et al. Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature. 2010 Jun 24;465(7301):1079–83.
Iannacone, Matteo, et al. “Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus.Nature, vol. 465, no. 7301, June 2010, pp. 1079–83. Pubmed, doi:10.1038/nature09118.
Iannacone M, Moseman EA, Tonti E, Bosurgi L, Junt T, Henrickson SE, Whelan SP, Guidotti LG, von Andrian UH. Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature. 2010 Jun 24;465(7301):1079–1083.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

June 24, 2010

Volume

465

Issue

7301

Start / End Page

1079 / 1083

Location

England

Related Subject Headings

  • Vesiculovirus
  • Vesicular stomatitis New Jersey virus
  • Vesicular stomatitis Indiana virus
  • Survival Rate
  • Rhabdoviridae Infections
  • Receptor, Interferon alpha-beta
  • Peripheral Nerves
  • Paralysis
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C