{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:46:21Z","timestamp":1785408381887,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,13]]},"group-title":"Molecular Biology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["R01AI151295"],"award-info":[{"award-number":["R01AI151295"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chagas disease is a major protozoan infection in the Americas, causing approximately 12,000 deaths each year. It is caused by\n                  <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                  , and can be transmitted transplacentally, leading to congenital Chagas disease, a silent route that carries substantial risk for newborns. However, the mechanisms underlying congenital Chagas transmission are poorly understood. Here, we evaluated whether\n                  <jats:italic>T. cruzi<\/jats:italic>\n                  infection alters the placental microenvironment and systemic physiology, and whether such alterations are associated with congenital transmission. Integrating bulk RNA sequencing, proteomics, and spatial transcriptomics, we show that\n                  <jats:italic>T. cruzi<\/jats:italic>\n                  infection elicits profound molecular remodeling in both placenta and peripheral blood, regardless of transmission status. Transmitting mothers exhibit a distinct transcriptional signature enriched for inflammatory and tissue-remodeling pathways. Notably, peripheral blood profiles mirrored some placental alterations. A panel of inflammatory serum proteins showed promising predictive potential for transmission risk, with implications for prenatal monitoring. Together, these findings support a fundamental shift in the conceptual framework of congenital Chagas disease, from a transmission-centered model to one that recognizes infection-driven placental damage as a pathological spectrum and identifies peripheral blood as a promising, non-invasive source of predictive biomarkers for adverse pregnancy outcomes. This framework motivates the further application of single-cell-resolution approaches to refine models of congenital Chagas pathogenesis and the systematic analysis of maternal peripheral blood during pregnancy to enable early risk stratification and the development of predictive tools for adverse outcomes.\n                <\/jats:p>","DOI":"10.64898\/2026.01.13.699142","type":"posted-content","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:30:15Z","timestamp":1768368615000},"source":"Crossref","is-referenced-by-count":0,"title":["Maternal\n                  <i>Trypanosoma cruzi<\/i>\n                  infection is associated with significant placental remodeling regardless of vertical transmission"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9329-0067","authenticated-orcid":false,"given":"Sneider Alexander Gutierrez","family":"Guarnizo","sequence":"first","affiliation":[{"name":"Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2775-2811","authenticated-orcid":false,"given":"Jaime","family":"So","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-3858","authenticated-orcid":false,"given":"Carolina","family":"Duque","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Samame","sequence":"additional","affiliation":[{"name":"Hospital Percy Boland Rodr\u00edguez, Ministerio de Salud, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1014-4497","authenticated-orcid":false,"given":"Jean Karla","family":"Velarde","sequence":"additional","affiliation":[{"name":"Hospital Percy Boland Rodr\u00edguez, Ministerio de Salud, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0471-5698","authenticated-orcid":false,"given":"Emily","family":"Arteaga","sequence":"additional","affiliation":[{"name":"Hospital Percy Boland Rodr\u00edguez, Ministerio de Salud, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clariza","family":"Roxana","sequence":"additional","affiliation":[{"name":"Hospital Percy Boland Rodr\u00edguez, Ministerio de Salud, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3206-4204","authenticated-orcid":false,"given":"Luciana","family":"Basma","sequence":"additional","affiliation":[{"name":"Hospital Percy Boland Rodr\u00edguez, Ministerio de Salud, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liseth","family":"Roque","sequence":"additional","affiliation":[{"name":"Hospital Percy Boland Rodr\u00edguez, Ministerio de Salud, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessy","family":"Condori","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Laboratory, Department of Cellular and Molecular Sciences, Universidad Peruana Cayetano Heredia, Lima, Per\u00fa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-6091","authenticated-orcid":false,"given":"Mart\u00edn","family":"Obreg\u00f3n","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Laboratory, Department of Cellular and Molecular Sciences, Universidad Peruana Cayetano Heredia, Lima, Per\u00fa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-6655","authenticated-orcid":false,"given":"Edith","family":"Malaga","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Laboratory, Department of Cellular and Molecular Sciences, Universidad Peruana Cayetano Heredia, Lima, Per\u00fa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4315-737X","authenticated-orcid":false,"given":"Jill","family":"Hakim","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenice","family":"Harrison","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rony","family":"Colanzi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Japon\u00e9s, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Verastegui","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Laboratory, Department of Cellular and Molecular Sciences, Universidad Peruana Cayetano Heredia, Lima, Per\u00fa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Pajuelo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Laboratory, Department of Cellular and Molecular Sciences, Universidad Peruana Cayetano Heredia, Lima, Per\u00fa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-2637","authenticated-orcid":false,"given":"Freddy","family":"Tinajeros","sequence":"additional","affiliation":[{"name":"Hospital Percy Boland Rodr\u00edguez, Ministerio de Salud, Santa Cruz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3704-9217","authenticated-orcid":false,"given":"Robert","family":"Gilman","sequence":"additional","affiliation":[{"name":"Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4260-8009","authenticated-orcid":false,"given":"Natalie","family":"Bowman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-2530","authenticated-orcid":false,"given":"Monica R.","family":"Mugnier","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Chagas Disease Working Group in Bolivia and Peru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020510585510000_2026.01.13.699142v1.1","unstructured":"CDC. Parasites - American Trypanosomiasis (also known as Chagas Disease). (2021)."},{"key":"2026020510585510000_2026.01.13.699142v1.2","unstructured":"WHO. Chagas disease (also known as American trypanosomiasis). https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)#:\u223c:text=Chagas%20disease%2C%20also%20known%20as,cruzi . (2023)."},{"key":"2026020510585510000_2026.01.13.699142v1.3","unstructured":"3. WHO. 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High production of pro-inflammatory cytokines by maternal blood mononuclear cells is associated with reduced maternal malaria but increased cord blood infection. Malar J 17, 177 (2018).","DOI":"10.1186\/s12936-018-2317-2"},{"key":"2026020510585510000_2026.01.13.699142v1.36","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2268-0"},{"key":"2026020510585510000_2026.01.13.699142v1.37","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.1.152-159.2006"},{"key":"2026020510585510000_2026.01.13.699142v1.38","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1021\/acsinfecdis.2c00318","article-title":"Trypanosoma cruzi Infection Promotes Vascular Remodeling and Coexpression of \u03b1-Smooth Muscle Actin and Macrophage Markers in Cells of the Aorta","volume":"8","year":"2022","journal-title":"ACS Infect. 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