{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:45:30Z","timestamp":1790808330340,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03b2 signaling in astrocytes is of particular interest because TGF-\u03b2 is universally upregulated during CNS infection and serves master regulatory and primarily anti-inflammatory functions. We report in this study that TGF-\u03b2 signaling is activated in astrocytes during toxoplasmic encephalitis and that inhibition of astrocytic TGF-\u03b2 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-\u03b2 signaling are independent of parasite burden and the ability of GFAP+ astrocytes to physically encircle parasites.<\/jats:p>","DOI":"10.4049\/jimmunol.1303284","type":"journal-article","created":{"date-parts":[[2014,5,24]],"date-time":"2014-05-24T05:51:48Z","timestamp":1400910708000},"page":"139-149","source":"Crossref","is-referenced-by-count":130,"title":["Astrocytic TGF-\u03b2 Signaling Limits Inflammation and Reduces Neuronal Damage during Central Nervous System <i>Toxoplasma<\/i> Infection"],"prefix":"10.1093","volume":"193","author":[{"given":"Egle","family":"Cekanaviciute","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"},{"name":"Neurosciences Graduate Program, Stanford Neurosciences Institute, Stanford University , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans K","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Stanford University , Stanford, CA 94305"},{"name":"BIO5 Institute, University of Arizona , Tucson, AZ 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Axtell","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riann","family":"Egusquiza","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M","family":"Wai","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita A","family":"Koshy","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"},{"name":"Division of Infectious Diseases, Department of Medicine, Stanford University , Stanford, CA 94305"},{"name":"BIO5 Institute, University of Arizona , Tucson, AZ 85721"},{"name":"Department of Neurology, University of Arizona , Tucson, AZ 85721"},{"name":"Department of Immunobiology, University of Arizona , Tucson, AZ 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion S","family":"Buckwalter","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"},{"name":"Department of Neurosurgery, Stanford University , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,7,1]]},"reference":[{"key":"2025030707191228700_r1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.it.2007.01.005","article-title":"Astrocytes are active players in cerebral innate immunity","volume":"28","author":"Farina","year":"2007","journal-title":"Trends Immunol."},{"key":"2025030707191228700_r2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nri3265","article-title":"The anatomical and cellular basis of immune surveillance in the central nervous system","volume":"12","author":"Ransohoff","year":"2012","journal-title":"Nat. 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