{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T06:51:40Z","timestamp":1758264700634,"version":"3.38.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"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":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-\u03b1, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas Toxoplasma gondii is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-\u03b1 in response to viral stimulation. In this study, we investigated the impact of coinfection with T. gondii on the innate virus-directed responses of human pDCs. Using intracellular flow cytometry and fluorescence microscopy, we determined that T. gondii invaded but did not induce IFN-\u03b1 or TNF-\u03b1 in human pDC. However, T. gondii inhibited IFN-\u03b1 and TNF-\u03b1 produced in response to HSV and HIV, thus functionally inactivating pDC. IFN-\u03b1 production was inhibited only in cells infected by T. gondii, which inhibited neither uptake of GFP-HSV nor localization of TLR9 in CD71+ endosomes, directing us to investigate downstream events. Using imaging flow cytometry, we found that both T. gondii and IL-10 inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN response factor 7. Blockade of IFN response factor 7 nuclear translocation and inhibition of the IFN-\u03b1 response was partially reversed by a deficiency in the T. gondii\u2013derived ROP16 kinase, known to directly phosphorylate STAT3, a critical mediator of IL-10\u2019s anti-inflammatory effects. Taken together, our results indicate that T. gondii suppresses pDC activation by mimicking IL-10\u2019s regulatory effects through an ROP16 kinase-dependent mechanism. Our findings further imply a convergent mechanism of inhibition of TLR signaling by T. gondii and IL-10 and suggest potential negative consequences of HIV\/T. gondii coinfection.<\/jats:p>","DOI":"10.4049\/jimmunol.1701045","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T19:10:25Z","timestamp":1511809825000},"page":"186-195","source":"Crossref","is-referenced-by-count":20,"title":["<i>Toxoplasma gondii<\/i> Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-4107","authenticated-orcid":false,"given":"Piotr L","family":"Pierog","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School , Newark, NJ 07103"},{"name":"Center for Immunity and Inflammation, Rutgers New Jersey Medical School , Newark, NJ 07103"},{"name":"Rutgers School of Graduate Studies , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0278-7543","authenticated-orcid":false,"given":"Yanlin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, Rutgers New Jersey Medical School , Newark, NJ 07103"},{"name":"Department of Medicine, Rutgers New Jersey Medical School , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukhwinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School , Newark, NJ 07103"},{"name":"Center for Immunity and Inflammation, Rutgers New Jersey Medical School , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George S","family":"Yap","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, Rutgers New Jersey Medical School , Newark, NJ 07103"},{"name":"Rutgers School of Graduate Studies , Newark, NJ 07103"},{"name":"Department of Medicine, Rutgers New Jersey Medical School , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7604-3184","authenticated-orcid":false,"given":"Patricia","family":"Fitzgerald-Bocarsly","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School , Newark, NJ 07103"},{"name":"Center for Immunity and Inflammation, Rutgers New Jersey Medical School , Newark, NJ 07103"},{"name":"Rutgers School of Graduate Studies , Newark, NJ 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,1,1]]},"reference":[{"key":"2025030610004242900_r1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.cytogfr.2007.10.006","article-title":"Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history","volume":"19","author":"Fitzgerald-Bocarsly","year":"2008","journal-title":"Cytokine Growth Factor Rev."},{"key":"2025030610004242900_r2","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/nature03464","article-title":"IRF-7 is the master regulator of type-I interferon-dependent immune responses","volume":"434","author":"Honda","year":"2005","journal-title":"Nature"},{"key":"2025030610004242900_r3","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1189\/jlb.0603255","article-title":"Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells","volume":"74","author":"Izaguirre","year":"2003","journal-title":"J. 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