The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells
Open accessAbstract
Group A streptococcal (GAS) infection induces the production of Abs that cross-react with host neuronal proteins, and these anti-GAS mimetic Abs are associated with autoimmune diseases of the CNS. However, the mechanisms that allow these Abs to cross the blood-brain barrier (BBB) and induce neuropathology remain unresolved. We have previously shown that GAS infection in mouse models induces a robust Th17 response in nasal-associated lymphoid tissue (NALT). Here, we identified GAS-specific Th17 cells in tonsils of humans naturally exposed to GAS, prompting us to explore whether GAS-specific CD4+ T cells home to mouse brains following i.n. infection. Intranasal challenge of repeatedly GAS-inoculated mice promoted migration of GAS-specific Th17 cells from NALT into the brain, BBB breakdown, serum IgG deposition, microglial activation, and loss of excitatory synaptic proteins under conditions in which no viable bacteria were detected in CNS tissue. CD4+ T cells were predominantly located in the olfactory bulb (OB) and in other brain regions that receive direct input from the OB. Together, these findings provide insight into the immunopathology of neuropsychiatric complications that are associated with GAS infections and suggest that crosstalk between the CNS and cellular immunity may be a general mechanism by which infectious agents exacerbate symptoms associated with other CNS autoimmune disorders.
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“The pathophysiology of IAE is believed to involve an autoimmune process that targets brain structures including the basal ganglia, leading to neuroinflammation and subsequent neuropsychiatric symptoms.”
From An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know (2023) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Streptococcus-specific T H 17 cells in the CNS that remain after repeated intranasal infections increase permeability of capillaries in proximity to the olfactory bulb, amygdala, and hypothalamus.”
From An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know (2023) · cites this paper as [15]
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“This causes disruption of tight junctions that are essential to maintaining the integrity of the BBB, allowing infiltration with immunoglobulin (Ig) G and anti-CNS autoantibodies.15”
From An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know (2023) · cites this paper as [15]
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“Mouse models currently indicate how intranasal infections with bacteria can polarize T cells toward a T H 17 phenotype owing to production of 2 proinflammatory cytokines, interleukin (IL)-6, and transforming growth factor-b1.15”
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Metadata
- Authors
- Dileepan, T., Smith, E. D., Knowland, D., Hsu, M., Platt, M., Bittner-Eddy, P., Cohen, B., Southern, P., Latimer, E., Harley, E., Agalliu, D., & Cleary, P. P.
- Affiliations
- University of Minnesota (US)
- University of California, Irvine (US)
- Columbia University Irving Medical Center (US)
- Georgetown University (US)
- Corresponding author
- Agalliu, Dritan
- Cleary, P. Patrick
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2015-12-14
- Volume
- 126
- Issue
- 1
- Pages
- 303-317
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC4701547
- OpenAlex
- W2208060404
- Cited by
- 128
- References
- 64
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 9 · 2023: 18 · 2022: 12 · 2021: 9 · 2020: 13 · 2019: 9 · 2018: 6 · 2017: 18 · 2016: 10
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Multiple Sclerosis Society (RG4673A1/1)
- University of Minnesota
- Multiple Sclerosis Society
- National Institutes of Health (CA-62203)
- University of California, Irvine (CA-62203)
- National Heart, Lung, and Blood Institute (R01HL116995, HL116995-01)
- National Cancer Institute (CA 62203, P30CA062203)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Streptococcal Infections and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- Streptococcus pyogenes, streptococcal infection, Th17 cells, intranasal infection, blood-brain barrier disruption, central nervous system autoimmunity, autoantibody cross-reactivity, nasal-associated lymphoid tissue, tonsil, CD4+ T cell migration, microglial activation, olfactory bulb, neuropsychiatric complications
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Cell Movement, Female, Immunoglobulin G, Interferon-gamma, Mice, Inbred C57BL, Streptococcus pyogenes, Palatine Tonsil, CD4-Positive T-Lymphocytes, Tight Junctions, Interleukin-17, Mice, Th17 Cells
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