Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes

Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes Lijun Cui, Yu Wang, Liqin Ren, Zhidan Li, Yuzhu Jiang, Chao Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2092665/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: Toxoplasma gondii（T. gondii） infection during pregnancy can lead to fetal defect or congenital complications. The inhibitory molecule B7-H4 expressed on decidual macrophage (dMφ) exerted important role in maternal-fetal tolerance. However, the effect of B7-H4 on the function of dMφ during T. gondii infection remains unclear. Methods: In the present study, the change of B7-H4 expression on dMφ after T. gondii infection were explored in vivo and in vitro. B7-H4-/- pregnant mice and purified primary human dMφ treated by B7-H4 neutralizing antibody were used to explore the role of B7-H4 signaling on regulating the membrane molecules, arginine metabolic enzymes synthesis, and cytokines production of dMφ with T. gondii infection. Also adoptive transfer of dMφ from WT pregnant mice or B7-H4-/- pregnant mice to infected B7-H4-/- pregnant mice were used to examine the effect of B7-H4 on adverse pregnancy outcomes induced by T. gondii infection. Results: Our results illustrated that B7-H4-/- pregnant mice infected by T. gondii displayed poorer pregnancy outcomes than those of the wild-type counterparts. B7-H4 expression on dMφ significantly decreased after T. gondii infection, which further resulted in the polarization of dMφ from M2 toward M1 phenotype by changing the expression of membrane molecules (CD80, CD86, CD163, CD206), arginine metabolic enzymes (Arg-1, iNOS) synthesis, and cytokines (IL-10, TNF-α) production. Also, we found that the B7-H4 down-regulation after T. gondii infection increased iNOS and TNF-α expression through JAK2/STAT1 signaling pathway. Besides, adoptive transfer of dMφ from WT pregnant mice donor rather than B7-H4-/- pregnant mice donor could improve adverse pregnancy outcomes induced by T. gondii infection. Conclusions: The results demonstrated that the downregulation of B7-H4 induced by T. gondii infection leaded to the dysfunction of decidual macrophages and contributed to abnormal pregnancy outcomes. Moreover, adoptive transfer of B7-H4+dMφ could improve adverse pregnancy outcomes induced by T. gondii infection. Toxoplasma gondii decidual macrophage B7-H4 abnormal pregnancy adoptive transfer Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Full Text Additional Declarations No competing interests reported. Supplementary Files Additionalfile1TextS1.Supplementaryofmethod.pdf Additionalfile2FigureS1.tif Additionalfile3FigureS2.tif Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 04 Oct, 2022 Reviews received at journal 03 Oct, 2022 Reviewers agreed at journal 27 Sep, 2022 Reviewers invited by journal 27 Sep, 2022 Editor assigned by journal 23 Sep, 2022 Submission checks completed at journal 22 Sep, 2022 First submitted to journal 22 Sep, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2092665","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":138921712,"identity":"d9a803c1-1e0e-4200-a6f2-2eaeb74fe103","order_by":0,"name":"Lijun Cui","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lijun","middleName":"","lastName":"Cui","suffix":""},{"id":138921713,"identity":"dbe445f6-0d6a-4871-9e62-3f6c5bf57148","order_by":1,"name":"Yu Wang","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Wang","suffix":""},{"id":138921714,"identity":"586841c9-cf43-4a81-8c7d-a5f4476405bd","order_by":2,"name":"Liqin Ren","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liqin","middleName":"","lastName":"Ren","suffix":""},{"id":138921715,"identity":"9a9924c5-1411-44b2-92f2-264670dc2fa0","order_by":3,"name":"Zhidan Li","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhidan","middleName":"","lastName":"Li","suffix":""},{"id":138921716,"identity":"83f3a0d6-babe-49b0-adf6-6e88f550096d","order_by":4,"name":"Yuzhu Jiang","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuzhu","middleName":"","lastName":"Jiang","suffix":""},{"id":138921717,"identity":"3e5a616d-8311-4beb-a637-4c4e38aa8f5e","order_by":5,"name":"Chao Wang","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chao","middleName":"","lastName":"Wang","suffix":""},{"id":138921718,"identity":"c2c3db6a-33c1-483c-bc1d-00fff3b45809","order_by":6,"name":"Xianbing Liu","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xianbing","middleName":"","lastName":"Liu","suffix":""},{"id":138921719,"identity":"4a6d90f5-259d-4e5a-8d40-cccdaf72e33e","order_by":7,"name":"Yushan Ren","email":"","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yushan","middleName":"","lastName":"Ren","suffix":""},{"id":138921720,"identity":"af1ac107-edc7-4146-be0d-45c743aee14d","order_by":8,"name":"Xuemei Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYPACCQYDBuYDBz78IE0LW+LBmT2k2GPAwGN8mIONGJU3kg8w3aiwYDCXyPlwmIGHQZ5f7AB+LZIz0hKYc85IMFjOyN1wuMCCwXDm7AT8Wvglcsx/57ZJ1G+4AdQyg4chweA2AS1sEvkfmHP/Ab1/I+fBYR42IrQAbWFgzm0Aa2EgTotkzzMD5pxjQC1nnhkAA1mCsF8Mjic/YM6pqQMxHn/48MNGnl+agBZ0IEGa8lEwCkbBKBgF2AEADZVAAonLlDEAAAAASUVORK5CYII=","orcid":"","institution":"Binzhou Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xuemei","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2022-09-22 12:14:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2092665/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2092665/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":27043601,"identity":"b6ea4f2b-22ed-49e9-8e1f-69adb8692aba","added_by":"auto","created_at":"2022-09-27 17:09:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2969923,"visible":true,"origin":"","legend":"\u003cp\u003eEffects of B7-H4 on pregnancy outcomes during T. gondii infection in mice. (a-c) Pregnancy outcomes: mice, uterus, placentas, and fetuses in uninfected, infected, and B7-H4-/- infected groups. (d) Placental and fetal weight, stillbirth rates and resorption rates were analyzed in uninfected, infected, and B7-H4-/- infected groups. (e) SEM showing the different fetal development situations in the uninfected, infected, and B7-H4-/- infected groups. (f) HE staining of uninfected, infected, and B7-H4-/- infected mouse placentas. Obvious hemorrhaging are shown by arrows. Scale bar: 100 μm. Data are presented as means ±SD, at least eight pregnant mice in each group were assayed individually by unpaired t-test, *p \u0026lt; 0.05, **p \u0026lt; 0.01.\u0026nbsp;\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/e1744e60cc48bbba32ae2b5c.png"},{"id":27042494,"identity":"67dc9348-c633-4577-b087-2227ee712412","added_by":"auto","created_at":"2022-09-27 17:04:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":851524,"visible":true,"origin":"","legend":"\u003cp\u003eChanges of B7-H4 expression on decidual macrophages and its effection on Phagocytic activities during T. gondii infection. (a) Expression levels of B7-H4 on 8human CD14+ dMφ in uninfected, infected, and B7-H4 neutralized infected groups detected by flow cytometry. (b) B7-H4 expression on mouse F4/80+ dMφ detected in 8uninfected, infected, and B7-H4-/- infected mice by flow cytometry. (c) Fluorescence microscopy was used to observe and record the number of phagocytic dMφ in the uninfected, infected, and B7-H4 neutralized infected groups. (d) Flow cytometry results showing the phagocytotic capacity of dMφ in the uninfected, infected, and B7- H4 neutralized infected groups. Data are presented as means ±SD, at least six pregnant mice or human samples in each group were assayed individually by unpaired t-test, *p \u0026lt; 0.05, **p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/f286b22ef4012034b035d49a.png"},{"id":27042491,"identity":"fa0af64e-ef09-4361-9ac7-722fc3eeb7f6","added_by":"auto","created_at":"2022-09-27 17:04:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1230203,"visible":true,"origin":"","legend":"\u003cp\u003eReduction of B7-H4 expression on decidual macrophages by T. gondii infection affects the expression of M1 and M2 membrane functional molecules. (a-e) Flow cytometry analysis of CD80, CD86, CD206 and CD163 levels on human dMφ in uninfected, infected, and B7-H4 neutralized infected groups. (f-i) Flow cytometry analysis of B7-H4, CD80, CD86, and CD206 expressions on dMφ in uninfected, infected, and B7-H4-/- infected mice. Data are presented as means ±SD, at least six pregnant mice or human samples in each group were assayed individually by unpaired t-test, *p \u0026lt; 0.05, **p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/d7f2871b2fc1aea239888693.png"},{"id":27042498,"identity":"54f9be22-912b-4aef-afd0-2854c17a2ede","added_by":"auto","created_at":"2022-09-27 17:04:37","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":298992,"visible":true,"origin":"","legend":"\u003cp\u003eReduction of B7-H4 expression on decidual macrophages with T. gondii infection resulted in the expression changes of iNOS and Arg-1. (a) Levels of Arg-1 produced by dMφ in uninfected, infected, and B7-H4-/- infected mice analyzed by flow cytometry. (b) Flow cytometry analysis of iNOS produced by dMφ in uninfected, infected, and B7-H4-/- infected mice. (c) Western blotting assay of B7-H4, iNOS, and Arg-1 protein levels in uninfected, infected, and B7-H4 neutralized infected groups of purified human macrophages. Data are presented as means ± SD, and differences were identified by unpaired t-test; (*P \u0026lt; 0.05). Data are presented as means ±SD, at least six pregnant mice or human samples in each group were assayed individually by unpaired t-test, *p \u0026lt; 0.05, **p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/5b982d22b77c904cb388e9fc.png"},{"id":27042495,"identity":"b5194893-e6fc-4767-9866-5c19ee6af86a","added_by":"auto","created_at":"2022-09-27 17:04:37","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":694716,"visible":true,"origin":"","legend":"\u003cp\u003eReduction of B7-H4 expression on decidual macrophages with T. gondii infection resulted in the expression changes of TNF-α and IL-10. (a-c) Expression level of IL-10 and TNF-α in F4/80+ dMφ in uninfected, infected, and B7-H4-/- infected mice detected by flow cytometry. (d, e) Western blotting assay of TNF-α and IL-10 levels in CD14+ dMφ of the uninfected, infected, and B7-H4 neutralized infected groups. (f, g) Representative immunofluorescent photographs of B7-H4, TNF-α, and IL-10 of CD14+ dMφ in the uninfected, infected, and B7-H4 neutralized infected groups. Data are presented as means ±SD, at least six pregnant mice or human samples in each group were assayed individually by unpaired t-test, *p \u0026lt; 0.05, **p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/e498e9ff9c4de1f3818d0713.png"},{"id":27042497,"identity":"7796e684-f6a7-4a4c-9bea-bee051b2aa35","added_by":"auto","created_at":"2022-09-27 17:04:37","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":487605,"visible":true,"origin":"","legend":"\u003cp\u003eDownregulation of B7-H4 by T. gondii infection resulted in changes in the decidual macrophage function by affecting the JAK2/STAT1 signaling pathways. (a,b) Representative western blot and histograms analysis of B7-H4, JAK2, p-JAK2, STAT1, and p-STAT1 levels of dMφ in uninfected, infected, and B7-H4 neutralized infected groups. (c, d) Representative western blot and histograms analysis of B7-H4, STAT1, p-STAT1, iNOS, and TNF-α of dMφ in the uninfected, infected, infected plus STAT1 inhibitor, B7-H4 neutralized infected, and B7-H4 neutralized infected plus STAT1 inhibitor groups. The data in all panels are a representative of at least three independent experiments. Data are presented as means ±SD, unpaired t-test, *p \u0026lt; 0.05, **p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/5feeb977a7e9ad86d2dab102.png"},{"id":27043599,"identity":"d44f3ea3-d379-4df0-a5a2-e112689525bb","added_by":"auto","created_at":"2022-09-27 17:09:36","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":956642,"visible":true,"origin":"","legend":"\u003cp\u003eAdoptive transfer of decidual macrophages from WT mice alleviated the adverse pregnancy outcomes and reversed the dysfunction of decidual macrophage by T. gondii infection. (a-c) Pregnancy outcomes: 903 fetuses and placentas in the three groups. (d) Comparison of placenta, fetal weight, and abnormal fetal rate of pregnant mice in the three groups. (e) Proportion of CFSE+ macrophages in the placenta of transplanted mice. \u0026nbsp;(f) Level of B7-H4 on the surface of dMφ in the three groups. (g, h) Flow cytometry was used to detect the expression of CD86 and CD206 in the three groups. (i) Detection of the expressions of Arg-1 and iNOS in the three groups by flow cytometry. (j, k) Detection of the expressions of IL-10 and TNF-α in the three groups by flow cytometry. Group 1: B7-H4-/- infected mice, Group 2: B7-H4-/- infected mice transferred with B7- H4-/- macrophages, and Group 3: B7-H4-/- infected mice transferred with WT macrophages. Data are presented as means ±SD, at least six pregnant mice or human samples in each group were assayed individually by unpaired t-test, *p \u0026lt; 0.05, **p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/aae6699672a03fc74d197463.png"},{"id":27044157,"identity":"7b0d0b9e-57d6-4c12-a9d8-49f248292769","added_by":"auto","created_at":"2022-09-27 17:14:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1275930,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript20220921.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1_covered.pdf"},{"id":27043602,"identity":"a6660e16-b83a-47f5-9f7e-27fa264c1f6b","added_by":"auto","created_at":"2022-09-27 17:09:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":183075,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1TextS1.Supplementaryofmethod.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/92b58b113d02649beff9eefe.pdf"},{"id":27043600,"identity":"b38ceb6b-e8a6-4704-8095-e8e45ac17b5e","added_by":"auto","created_at":"2022-09-27 17:09:37","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":431388,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile2FigureS1.tif","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/1e35a7a067bd852dee0fda74.tif"},{"id":27042492,"identity":"ed24f582-ce4c-409f-8387-f817b11016b8","added_by":"auto","created_at":"2022-09-27 17:04:36","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":903444,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile3FigureS2.tif","url":"https://assets-eu.researchsquare.com/files/rs-2092665/v1/00ddfed3ed614de49f4d74d6.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-2092665/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Toxoplasma gondii, decidual macrophage, B7-H4, abnormal pregnancy, adoptive transfer","lastPublishedDoi":"10.21203/rs.3.rs-2092665/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2092665/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background: Toxoplasma gondii（T. gondii） infection during pregnancy can lead to fetal defect or congenital complications. The inhibitory molecule B7-H4 expressed on decidual macrophage (dMφ) exerted important role in maternal-fetal tolerance. However, the effect of B7-H4 on the function of dMφ during T. gondii infection remains unclear.\nMethods: In the present study, the change of B7-H4 expression on dMφ after T. gondii infection were explored in vivo and in vitro. B7-H4-/- pregnant mice and purified primary human dMφ treated by B7-H4 neutralizing antibody were used to explore the role of B7-H4 signaling on regulating the membrane molecules, arginine metabolic enzymes synthesis, and cytokines production of dMφ with T. gondii infection. Also adoptive transfer of dMφ from WT pregnant mice or B7-H4-/- pregnant mice to infected B7-H4-/- pregnant mice were used to examine the effect of B7-H4 on adverse pregnancy outcomes induced by T. gondii infection.\nResults: Our results illustrated that B7-H4-/- pregnant mice infected by T. gondii displayed poorer pregnancy outcomes than those of the wild-type counterparts. B7-H4 expression on dMφ significantly decreased after T. gondii infection, which further resulted in the polarization of dMφ from M2 toward M1 phenotype by changing the expression of membrane molecules (CD80, CD86, CD163, CD206), arginine metabolic enzymes (Arg-1, iNOS) synthesis, and cytokines (IL-10, TNF-α) production. Also, we found that the B7-H4 down-regulation after T. gondii infection increased iNOS and TNF-α expression through JAK2/STAT1 signaling pathway. Besides, adoptive transfer of dMφ from WT pregnant mice donor rather than B7-H4-/- pregnant mice donor could improve adverse pregnancy outcomes induced by T. gondii infection.\nConclusions: The results demonstrated that the downregulation of B7-H4 induced by T. gondii infection leaded to the dysfunction of decidual macrophages and contributed to abnormal pregnancy outcomes. Moreover, adoptive transfer of B7-H4+dMφ could improve adverse pregnancy outcomes induced by T. gondii infection.","manuscriptTitle":"Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-27 17:04:34","doi":"10.21203/rs.3.rs-2092665/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-10-04T12:33:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-10-03T12:37:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"aa0f5ad2-ec2b-4593-b7c3-db7a90c3b538_SNPRID","date":"2022-09-27T18:15:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-09-27T07:41:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-09-23T09:26:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-09-23T03:51:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Parasites \u0026 Vectors","date":"2022-09-22T12:04:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"19f1c311-d8b8-4796-83cf-dd9322ad945b","owner":[],"postedDate":"September 27th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-10-20T14:59:18+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-27 17:04:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2092665","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2092665","identity":"rs-2092665","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}