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A most-studied mechanism underlying innate immunity in<jats:named-content content-type=\"genus-species\">T. cruzi<\/jats:named-content>infection is Toll-like receptor (TLR) activation by lipids and other parasite molecules. However, yet-to-be-identified pathways should exist. Here, we show that<jats:named-content content-type=\"genus-species\">T. cruzi<\/jats:named-content>strongly upregulates monocyte chemoattractant protein 1 (MCP-1)\/CCL2 and fractalkine (FKN)\/CX3CL1 in cellular and mouse models of heart infection. Mechanistically, upregulation of MCP-1 and FKN stems from the interaction of parasite-derived neurotrophic factor (PDNF)\/<jats:italic>trans<\/jats:italic>-sialidase with neurotrophic receptors TrkA and TrkC, as assessed by pharmacological inhibition, neutralizing antibodies, and gene silencing studies. Administration of a single dose of intravenous PDNF to naive mice results in a dose-dependent increase in MCP-1 and FKN in the heart and liver with pulse-like kinetics that peak at 3 h postinjection. Intravenous PDNF also augments MCP-1 and FKN in TLR signaling-deficient MyD88-knockout mice, underscoring the MyD88-independent action of PDNF. Although single PDNF injections do not increase MCP-1 and FKN receptors, multiple PDNF injections at short intervals up the levels of receptor transcripts in the heart and liver, suggesting that sustained PDNF triggers cell recruitment at infection sites. Thus, given that MCP-1 and FKN are chemokines essential to the recruitment of immune cells to combat inflammation triggers and to enhance tissue repair, our findings uncover a new mechanism in innate immunity against<jats:named-content content-type=\"genus-species\">T. cruzi<\/jats:named-content>infection mediated by Trk signaling akin to an endogenous inflammatory and fibrotic pathway resulting from cardiomyocyte-TrkA recognition by matricellular connective tissue growth factor (CTGF\/CCN2).<\/jats:p>","DOI":"10.1128\/iai.02098-14","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T02:44:12Z","timestamp":1402973052000},"page":"3687-3696","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Parasite-Derived Neurotrophic Factor\/<i>trans<\/i>-Sialidase of Trypanosoma cruzi Links Neurotrophic Signaling to Cardiac Innate Immune Response"],"prefix":"10.1128","volume":"82","author":[{"given":"Ryan","family":"Salvador","sequence":"first","affiliation":[{"name":"Graduate Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University, and Department of Developmental, Biochemical and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Aridgides","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University, and Department of Developmental, Biochemical and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercio","family":"PereiraPerrin","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University, and Department of Developmental, Biochemical and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.624296"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60061-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-012-0351-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5273(97)02952-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000711"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1590\/S1020-49892009000100012"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002469"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.2.692-696.1994"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.1961-1967.1996"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"5890","DOI":"10.4049\/jimmunol.158.12.5890","article-title":"Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages","volume":"158","author":"Camargo MM","year":"1997","unstructured":"CamargoMMAlmeidaICPereiraMEFergusonMATravassosLRGazzinelliRT. 1997. 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