A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection

• Published in: PloS one Vol. 11; no. 9; p. e0162132
• Main Authors: Fontana, Mary F., Baccarella, Alyssa, Craft, Joshua F., Boyle, Michelle J., McIntyre, Tara I., Wood, Matthew D., Thorn, Kurt S., Anidi, Chioma, Bayat, Aqieda, Chung, Me Ree, Hamburger, Rebecca, Kim, Chris Y., Pearman, Emily, Pham, Jennifer, Tang, Jia J., Boon, Louis, Kamya, Moses R., Dorsey, Grant, Feeney, Margaret E., Kim, Charles C.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.09.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Anemia; Animal models; Animals; Asymptomatic infection; Biology and Life Sciences; CD4 antigen; Child; Child, Preschool; Chronic Disease; Chronic infection; Disease Models, Animal; Exhaustion; Human behavior; Human subjects; Humans; Immune clearance; Immune response; Immune system; Immunity; Infant; Infections; Infectious diseases; Interleukin 10; Lymphocytes; Lymphocytes B; Lymphocytes T; Malaria; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Monocytes; Parasitemia; Parasitemia - parasitology; Parasites; Pathology; Persistent infection; Pharmacology; Plasmodium; Plasmodium chabaudi; Plasmodium chabaudi - isolation & purification; Plasmodium falciparum; Research and Analysis Methods; Vector-borne diseases; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0162132

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.