Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system toxoplasma infection

Egle Cekanaviciute, Hans K. Dietrich, Robert C. Axtell, Aaron M. Williams, Riann Egusquiza, Karen M. Wai, Anita A Koshy, Marion S. Buckwalter

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The balance between controlling infection and limiting inflammation is particularly precarious in the brain because of its unique vulnerability to the toxic effects of inflammation. Astrocytes have been implicated as key regulators of neuroinflammation in CNS infections, including infection with Toxoplasma gondii, a protozoan parasite that naturally establishes a chronic CNS infection in mice and humans. In CNS toxoplasmosis, astrocytes are critical to controlling parasite growth. They secrete proinflammatory cytokines and physically encircle parasites. However, the molecular mechanisms used by astrocytes to limit neuroinflammation during toxoplasmic encephalitis have not yet been identified. TGF-β signaling in astrocytes is of particular interest because TGF-β is universally upregulated during CNS infection and serves master regulatory and primarily anti-inflammatory functions. We report in this study that TGF-β signaling is activated in astrocytes during toxoplasmic encephalitis and that inhibition of astrocytic TGF-β signaling increases immune cell infiltration, uncouples proinflammatory cytokine and chemokine production from CNS parasite burden, and increases neuronal injury. Remarkably, we show that the effects of inhibiting astrocytic TGF-β signaling are independent of parasite burden and the ability of GFAP+ astrocytes to physically encircle parasites.

Original languageEnglish (US)
Pages (from-to)139-149
Number of pages11
JournalJournal of Immunology
Volume193
Issue number1
DOIs
StatePublished - Jul 1 2014

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Central Nervous System Infections
Toxoplasma
Astrocytes
Parasites
Inflammation
Toxoplasmosis
Encephalitis
Infection
Cytokines
Poisons
Chemokines
Anti-Inflammatory Agents
Wounds and Injuries
Brain
Growth

ASJC Scopus subject areas

  • Immunology

Cite this

Cekanaviciute, E., Dietrich, H. K., Axtell, R. C., Williams, A. M., Egusquiza, R., Wai, K. M., ... Buckwalter, M. S. (2014). Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system toxoplasma infection. Journal of Immunology, 193(1), 139-149. https://doi.org/10.4049/jimmunol.1303284

Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system toxoplasma infection. / Cekanaviciute, Egle; Dietrich, Hans K.; Axtell, Robert C.; Williams, Aaron M.; Egusquiza, Riann; Wai, Karen M.; Koshy, Anita A; Buckwalter, Marion S.

In: Journal of Immunology, Vol. 193, No. 1, 01.07.2014, p. 139-149.

Research output: Contribution to journalArticle

Cekanaviciute, E, Dietrich, HK, Axtell, RC, Williams, AM, Egusquiza, R, Wai, KM, Koshy, AA & Buckwalter, MS 2014, 'Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system toxoplasma infection', Journal of Immunology, vol. 193, no. 1, pp. 139-149. https://doi.org/10.4049/jimmunol.1303284
Cekanaviciute, Egle ; Dietrich, Hans K. ; Axtell, Robert C. ; Williams, Aaron M. ; Egusquiza, Riann ; Wai, Karen M. ; Koshy, Anita A ; Buckwalter, Marion S. / Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system toxoplasma infection. In: Journal of Immunology. 2014 ; Vol. 193, No. 1. pp. 139-149.
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