Examining the Reticulocyte Preference of Two Plasmodium berghei Strains during Blood-Stage Malaria Infection
The blood-stage of the parasite is one of the key phases within its life cycle that influences disease progression during a malaria infection. The efficiency of the parasite in infecting red blood cells (RBC) determines parasite load and parasite-induced hemolysis that is responsible for the develop...
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Published in | Frontiers in microbiology Vol. 9; p. 166 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
20.02.2018
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Subjects | |
Online Access | Get full text |
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Summary: | The blood-stage of the
parasite is one of the key phases within its life cycle that influences disease progression during a malaria infection. The efficiency of the parasite in infecting red blood cells (RBC) determines parasite load and parasite-induced hemolysis that is responsible for the development of anemia and potentially drives severe disease progression. However, the molecular factors defining the infectivity of
parasites have not been completely identified so far. Using the
mouse model for malaria, we characterized and compared the blood-stage infection dynamics of
ANKA WT and a mutant parasite strain lacking a novel
antigen,
maLS_05, that is well conserved in both human and animal
parasite strains. Infection of mice with parasites lacking
leads to lower parasitemia levels and less severe disease progression in contrast to mice infected with the wildtype
ANKA strain. To specifically determine the effect of deleting
on parasite infectivity we developed a mathematical model describing erythropoiesis and malarial infection of RBC. By applying our model to experimental data studying infection dynamics under normal and drug-induced altered erythropoietic conditions, we found that both
ANKA and
(-) parasite strains differed in their infectivity potential during the early intra-erythrocytic stage of infection. Parasites lacking
showed a decreased ability to infect RBC, and immature reticulocytes in particular that are usually a preferential target of the parasite. These altered infectivity characteristics limit parasite burden and affect disease progression. Our integrative analysis combining mathematical models and experimental data suggests that deletion of
affects productive infection of reticulocytes, which makes this antigen a useful target to analyze the actual processes relating RBC preferences to the development of severe disease outcomes in malaria. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present Address: Priyanka Fernandes, CIMI-Paris, National Institute for Health and Medical Research U1135, Faculté de Médecine Pierre et Marie Curie, Site Pitié Salpêtrière 5éme ètage, Paris, France Edited by: Ruy Ribeiro, Los Alamos National Laboratory (DOE), United States Reviewed by: Luis L. Fonseca, Georgia Institute of Technology, United States; Eberhard Otto Voit, Georgia Institute of Technology, United States This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology These authors have contributed equally to this work. |
ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2018.00166 |