دورية أكاديمية
Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5) In Vivo .
| العنوان: | Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5) In Vivo . |
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| المؤلفون: | Foquet L; Center for Infectious Disease Research, Seattle, WA, United States., Schafer C; Center for Infectious Disease Research, Seattle, WA, United States., Minkah NK; Center for Infectious Disease Research, Seattle, WA, United States., Alanine DGW; Jenner Institute, University of Oxford, Oxford, United Kingdom., Flannery EL; Center for Infectious Disease Research, Seattle, WA, United States., Steel RWJ; Center for Infectious Disease Research, Seattle, WA, United States., Sack BK; Center for Infectious Disease Research, Seattle, WA, United States., Camargo N; Center for Infectious Disease Research, Seattle, WA, United States., Fishbaugher M; Center for Infectious Disease Research, Seattle, WA, United States., Betz W; Center for Infectious Disease Research, Seattle, WA, United States., Nguyen T; Center for Infectious Disease Research, Seattle, WA, United States., Billman ZP; Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.; Department of Microbiology, University of Washington, Seattle, WA, United States., Wilson EM; Yecuris Corporation, Tualatin, OR, United States., Bial J; Yecuris Corporation, Tualatin, OR, United States., Murphy SC; Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.; Department of Microbiology, University of Washington, Seattle, WA, United States., Draper SJ; Jenner Institute, University of Oxford, Oxford, United Kingdom., Mikolajczak SA; Center for Infectious Disease Research, Seattle, WA, United States., Kappe SHI; Center for Infectious Disease Research, Seattle, WA, United States.; Department of Global Health, University of Washington, Seattle, WA, United States. |
| المصدر: | Frontiers in immunology [Front Immunol] 2018 Mar 14; Vol. 9, pp. 524. Date of Electronic Publication: 2018 Mar 14 (Print Publication: 2018). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Print ISSN: 1664-3224 (Print) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Disease Models, Animal* , Malaria, Falciparum*/parasitology, Animals ; Antibodies, Monoclonal/pharmacology ; Carrier Proteins/immunology ; Erythrocytes/parasitology ; Humans ; Liver Diseases/parasitology ; Mice, Knockout ; Parasitemia/parasitology ; Plasmodium falciparum ; Protozoan Proteins/immunology |
| مستخلص: | The invention of liver-humanized mouse models has made it possible to directly study the preerythrocytic stages of Plasmodium falciparum . In contrast, the current models to directly study blood stage infection in vivo are extremely limited. Humanization of the mouse blood stream is achievable by frequent injections of human red blood cells (hRBCs) and is currently the only system with which to study human malaria blood stage infections in a small animal model. Infections have been primarily achieved by direct injection of P. falciparum -infected RBCs but as such, this modality of infection does not model the natural route of infection by mosquito bite and lacks the transition of parasites from liver stage infection to blood stage infection. Including these life cycle transition points in a small animal model is of relevance for testing therapeutic interventions. To this end, we used FRGN KO mice that were engrafted with human hepatocytes and performed a blood exchange under immune modulation to engraft the animals with more than 50% hRBCs. These mice were infected by mosquito bite with sporozoite stages of a luciferase-expressing P. falciparum parasite, resulting in noninvasively measurable liver stage burden by in vivo bioluminescent imaging (IVIS) at days 5-7 postinfection. Transition to blood stage infection was observed by IVIS from day 8 onward and then blood stage parasitemia increased with a kinetic similar to that observed in controlled human malaria infection. To assess the utility of this model, we tested whether a monoclonal antibody targeting the erythrocyte invasion ligand reticulocyte-binding protein homolog 5 (with known growth inhibitory activity in vitro ) was capable of blocking blood stage infection in vivo when parasites emerge from the liver and found it highly effective. Together, these results show that a combined liver-humanized and blood-humanized FRGN mouse model infected with luciferase-expressing P. falciparum will be a useful tool to study P. falciparum preerythrocytic and erythrocytic stages and enables the testing of interventions that target either one or both stages of parasite infection. |
| References: | Int J Exp Pathol. 2004 Jun;85(3):147-57. (PMID: 15255968) PLoS One. 2008 May 21;3(5):e2252. (PMID: 18493601) Nat Methods. 2015 Jul;12(7):631-3. (PMID: 26030447) Hum Vaccin Immunother. 2012 Jun;8(6):706-14. (PMID: 22508415) Stem Cell Reports. 2016 Oct 11;7(4):591-601. (PMID: 27618723) Sci Rep. 2016 Oct 12;6:35025. (PMID: 27731362) PLoS One. 2015 Jun 22;10(6):e0129825. (PMID: 26098918) Malar J. 2014 Sep 30;13:386. (PMID: 25266106) Malar J. 2013 Nov 24;12:430. (PMID: 24267791) Nat Immunol. 2007 Dec;8(12):1313-23. (PMID: 17982459) NPJ Vaccines. 2017 Oct 9;2:27. (PMID: 29263882) Antimicrob Agents Chemother. 2009 Oct;53(10):4533-6. (PMID: 19596869) J Infect Dis. 2016 Jun 1;213(11):1743-51. (PMID: 26908756) Nat Genet. 1996 Mar;12(3):266-73. (PMID: 8589717) Mol Ther. 2011 Dec;19(12):2269-76. (PMID: 21862998) Nat Biotechnol. 2007 Aug;25(8):903-10. (PMID: 17664939) JCI Insight. 2017 Nov 2;2(21):null. (PMID: 29093263) Nat Biotechnol. 2014 Apr;32(4):364-72. (PMID: 24633240) PLoS One. 2012;7(2):e31208. (PMID: 22363582) Nat Commun. 2015 Jul 24;6:7690. (PMID: 26205537) Results Immunol. 2015 Dec 21;6:5-7. (PMID: 26870635) J Infect Dis. 2009 Apr 15;199(8):1151-4. (PMID: 19284307) PLoS One. 2011;6(5):e19826. (PMID: 21611197) Methods Enzymol. 2003;373:3-16. (PMID: 14714393) J Clin Invest. 2012 Oct;122(10):3618-28. (PMID: 22996664) Am J Trop Med Hyg. 2013 Jan;88(1):5-13. (PMID: 23149582) Cell Microbiol. 2012 Mar;14(3):316-24. (PMID: 22151703) Genes Dev. 1993 Dec;7(12A):2298-307. (PMID: 8253378) Antimicrob Agents Chemother. 2001 Jun;45(6):1847-53. (PMID: 11353636) |
| معلومات مُعتمدة: | MR/K017632/1 United Kingdom Medical Research Council; 106917/Z/15/Z United Kingdom Wellcome Trust |
| فهرسة مساهمة: | Keywords: Plasmodium falciparum; Plasmodium falciparum blood stages; clodronate liposomes; cyclophosphamide; humanized mouse model; reticulocyte-binding protein homolog 5 |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Carrier Proteins) 0 (Protozoan Proteins) 0 (RH5 protein, Plasmodium falciparum) |
| تواريخ الأحداث: | Date Created: 20180330 Date Completed: 20190510 Latest Revision: 20190510 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5861195 |
| DOI: | 10.3389/fimmu.2018.00524 |
| PMID: | 29593746 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2018.00524 |