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Deficient Natural Killer Dendritic Cell Responses Underlay the Induction of Theiler's Virus-Induced Autoimmunity.

Chastain EM, Getts DR, Miller SD - MBio (2015)

Bottom Line: Viral infection is an important cofactor, along with genetic susceptibility, in the initiation of a variety of organ-specific autoimmune diseases.Thus, in-depth understanding of how virus infections trigger autoimmunity may lead to novel ways to prevent or treat these diseases.Theiler's murine encephalitis virus-induced demyelinating disease (TMEV-IDD) serves as an important model for the human T cell-mediated autoimmune demyelinating disease multiple sclerosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

No MeSH data available.


Related in: MedlinePlus

Repopulation of TMEV-susceptible (B6 × SJL/J)F1 mice with B6 NKDCs induces CNS virus clearance. Spleens from naive WT (B6 × SJL/J)F1 mice were examined for the presence of NKDCs in comparison to WT B6 mice. (A) CD45+ CD11c+ cells were analyzed for expression of NK1.1 and DX5. (B) Six to 10 (B6 × SJL/J)F1 mice per group with our without adoptively transferred FACS-purified NKDCs from WT B6 mice were infected with TMEV or sham infected. The number of PFU in brain tissue was determined by plaque assay. *, P < 0.05.
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fig5: Repopulation of TMEV-susceptible (B6 × SJL/J)F1 mice with B6 NKDCs induces CNS virus clearance. Spleens from naive WT (B6 × SJL/J)F1 mice were examined for the presence of NKDCs in comparison to WT B6 mice. (A) CD45+ CD11c+ cells were analyzed for expression of NK1.1 and DX5. (B) Six to 10 (B6 × SJL/J)F1 mice per group with our without adoptively transferred FACS-purified NKDCs from WT B6 mice were infected with TMEV or sham infected. The number of PFU in brain tissue was determined by plaque assay. *, P < 0.05.

Mentions: Interestingly, analysis of the spleens of F1 mice showed that unlike SJL/J mice, they had a large population of NK cells (data not shown). Upon examination of their NKDC population, we observed they possessed significantly fewer NKDCs than B6 animals and also expressed much lower levels of NK1.1 (Fig. 5A). We thus hypothesized that F1 NKDCs were not as effective as B6 NKDCs given these constraints. In order to address our hypothesis, we tested if infusion of purified NKDCs from B6 donors would lead to CNS virus clearance in (B6 × SJL/J)F1 mice infected with TMEV. Viral titers were quantified using plaque assay on brain homogenates from day 7-infected F1 mice. Strikingly, F1 mice that had received an infusion of B6 NKDCs prior to infection had significantly less virus than noninfused F1 infected mice (Fig. 5B). These data therefore indicate that strain-specific generation of NKDCs is a critical factor in determining the capacity to effectively clear TMEV from the CNS.


Deficient Natural Killer Dendritic Cell Responses Underlay the Induction of Theiler's Virus-Induced Autoimmunity.

Chastain EM, Getts DR, Miller SD - MBio (2015)

Repopulation of TMEV-susceptible (B6 × SJL/J)F1 mice with B6 NKDCs induces CNS virus clearance. Spleens from naive WT (B6 × SJL/J)F1 mice were examined for the presence of NKDCs in comparison to WT B6 mice. (A) CD45+ CD11c+ cells were analyzed for expression of NK1.1 and DX5. (B) Six to 10 (B6 × SJL/J)F1 mice per group with our without adoptively transferred FACS-purified NKDCs from WT B6 mice were infected with TMEV or sham infected. The number of PFU in brain tissue was determined by plaque assay. *, P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4526717&req=5

fig5: Repopulation of TMEV-susceptible (B6 × SJL/J)F1 mice with B6 NKDCs induces CNS virus clearance. Spleens from naive WT (B6 × SJL/J)F1 mice were examined for the presence of NKDCs in comparison to WT B6 mice. (A) CD45+ CD11c+ cells were analyzed for expression of NK1.1 and DX5. (B) Six to 10 (B6 × SJL/J)F1 mice per group with our without adoptively transferred FACS-purified NKDCs from WT B6 mice were infected with TMEV or sham infected. The number of PFU in brain tissue was determined by plaque assay. *, P < 0.05.
Mentions: Interestingly, analysis of the spleens of F1 mice showed that unlike SJL/J mice, they had a large population of NK cells (data not shown). Upon examination of their NKDC population, we observed they possessed significantly fewer NKDCs than B6 animals and also expressed much lower levels of NK1.1 (Fig. 5A). We thus hypothesized that F1 NKDCs were not as effective as B6 NKDCs given these constraints. In order to address our hypothesis, we tested if infusion of purified NKDCs from B6 donors would lead to CNS virus clearance in (B6 × SJL/J)F1 mice infected with TMEV. Viral titers were quantified using plaque assay on brain homogenates from day 7-infected F1 mice. Strikingly, F1 mice that had received an infusion of B6 NKDCs prior to infection had significantly less virus than noninfused F1 infected mice (Fig. 5B). These data therefore indicate that strain-specific generation of NKDCs is a critical factor in determining the capacity to effectively clear TMEV from the CNS.

Bottom Line: Viral infection is an important cofactor, along with genetic susceptibility, in the initiation of a variety of organ-specific autoimmune diseases.Thus, in-depth understanding of how virus infections trigger autoimmunity may lead to novel ways to prevent or treat these diseases.Theiler's murine encephalitis virus-induced demyelinating disease (TMEV-IDD) serves as an important model for the human T cell-mediated autoimmune demyelinating disease multiple sclerosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

No MeSH data available.


Related in: MedlinePlus