TLR2 deficiency leads to increased Th17 infiltrates in experimental brain abscesses

Jessica R. Nichols, Amy L. Aldrich, Monica M. Mariani, Debbie Vidlak, Nilufer Esen, Tammy L Kielian

Research output: Contribution to journalArticle

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Abstract

TLR2 plays a pivotal role in recognizing Staphylococcus aureus, a common etiologic agent of CNS parenchymal infections, such as brain abscess. We previously reported that brain abscesses of TLR2 knockout (KO) mice exhibited elevated IL-17 levels, suggesting the presence of an alternative pathway available to respond to S. aureus infection that may involve Th17 cells. Both CD4+ and CD8+ T cell infiltrates were elevated in brain abscesses of TLR2 KO mice at days 3, 7, and 14 postinfection compared with wild-type animals. Intracellular cytokine staining revealed a significant increase in the frequency of IL-17-producing Th17 cells in TLR2 KO mice with relatively few IFN-γ-positive cells. γδ T cells were also a source of IL-17 in brain abscesses. Microglia, astrocytes, and macrophages were shown to express both IL-17RA and IL-17RC. Despite receptor expression, IL-17 was relatively ineffective at eliciting glial activation, whereas the cytokine augmented the ability of TNF-α to induce CXCL2 and CCL2 expression by macrophages. Based on the ability of IL-17 to elicit the release of chemokines and other proinflammatory mediators, we propose that the exaggerated IL-17 response that occurs in TLR2 KO mice functions in a compensatory manner to control brain abscess pathogenesis, with cells other than glia as targets for IL-17 action. This is supported by our findings in which innate immune infiltrates were not significantly different between TLR2 KO and wild-type mice in conjunction with the lack of prolonged alterations in the synthesis of other proinflammatory molecules during the course of infection.

Original languageEnglish (US)
Pages (from-to)7119-7130
Number of pages12
JournalJournal of Immunology
Volume182
Issue number11
DOIs
StatePublished - Jun 1 2009

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Brain Abscess
Interleukin-17
Knockout Mice
Th17 Cells
Neuroglia
Staphylococcus aureus
Infection
Macrophages
Cytokines
T-Lymphocytes
Wild Animals
Microglia
Chemokines
Astrocytes
Staining and Labeling

ASJC Scopus subject areas

  • Immunology

Cite this

TLR2 deficiency leads to increased Th17 infiltrates in experimental brain abscesses. / Nichols, Jessica R.; Aldrich, Amy L.; Mariani, Monica M.; Vidlak, Debbie; Esen, Nilufer; Kielian, Tammy L.

In: Journal of Immunology, Vol. 182, No. 11, 01.06.2009, p. 7119-7130.

Research output: Contribution to journalArticle

Nichols, Jessica R. ; Aldrich, Amy L. ; Mariani, Monica M. ; Vidlak, Debbie ; Esen, Nilufer ; Kielian, Tammy L. / TLR2 deficiency leads to increased Th17 infiltrates in experimental brain abscesses. In: Journal of Immunology. 2009 ; Vol. 182, No. 11. pp. 7119-7130.
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