A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection.
In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in underst...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5008831?pdf=render |
| _version_ | 1819100752960815104 |
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| author | Mary F Fontana Alyssa Baccarella Joshua F Craft Michelle J Boyle Tara I McIntyre Matthew D Wood Kurt S Thorn Chioma Anidi Aqieda Bayat Me Ree Chung Rebecca Hamburger Chris Y Kim Emily Pearman Jennifer Pham Jia J Tang Louis Boon Moses R Kamya Grant Dorsey Margaret E Feeney Charles C Kim |
| author_facet | Mary F Fontana Alyssa Baccarella Joshua F Craft Michelle J Boyle Tara I McIntyre Matthew D Wood Kurt S Thorn Chioma Anidi Aqieda Bayat Me Ree Chung Rebecca Hamburger Chris Y Kim Emily Pearman Jennifer Pham Jia J Tang Louis Boon Moses R Kamya Grant Dorsey Margaret E Feeney Charles C Kim |
| author_sort | Mary F Fontana |
| collection | DOAJ |
| description | In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection. |
| first_indexed | 2024-12-22T01:07:47Z |
| format | Article |
| id | doaj.art-9165e2b7d1b24afd951db53c44082b8f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:07:47Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9165e2b7d1b24afd951db53c44082b8f2022-12-21T18:44:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016213210.1371/journal.pone.0162132A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection.Mary F FontanaAlyssa BaccarellaJoshua F CraftMichelle J BoyleTara I McIntyreMatthew D WoodKurt S ThornChioma AnidiAqieda BayatMe Ree ChungRebecca HamburgerChris Y KimEmily PearmanJennifer PhamJia J TangLouis BoonMoses R KamyaGrant DorseyMargaret E FeeneyCharles C KimIn humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection.http://europepmc.org/articles/PMC5008831?pdf=render |
| spellingShingle | Mary F Fontana Alyssa Baccarella Joshua F Craft Michelle J Boyle Tara I McIntyre Matthew D Wood Kurt S Thorn Chioma Anidi Aqieda Bayat Me Ree Chung Rebecca Hamburger Chris Y Kim Emily Pearman Jennifer Pham Jia J Tang Louis Boon Moses R Kamya Grant Dorsey Margaret E Feeney Charles C Kim A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection. PLoS ONE |
| title | A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection. |
| title_full | A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection. |
| title_fullStr | A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection. |
| title_full_unstemmed | A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection. |
| title_short | A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection. |
| title_sort | novel model of asymptomatic plasmodium parasitemia that recapitulates elements of the human immune response to chronic infection |
| url | http://europepmc.org/articles/PMC5008831?pdf=render |
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