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Infection and Immunity, June 2006, p. 3204-3212, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.01560-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Babesia microti Primarily Invades Mature Erythrocytes in Mice

Ingo Borggraefe,^1, Jie Yuan,¹ Sam R. Telford III,² Sanjay Menon,¹ Rouette Hunter,³ Sohela Shah,⁴ Andrew Spielman,⁵ Jeffrey A. Gelfand,⁴ Henry H. Wortis,⁴ and Edouard Vannier^1*

Division of Geographic Medicine and Infectious Diseases,¹ Hematology Laboratory, Tufts-New England Medical Center,³ Department of Pathology, Tufts University School of Medicine,⁴ Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston,⁵ Division of Infectious Diseases, Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts²

Received 22 September 2005/ Returned for modification 3 November 2005/ Accepted 18 March 2006

Babesia microti is a tick-borne red blood cell parasite that causes babesiosis in people. Its most common vertebrate reservoir is the white-footed mouse. To determine whether B. microti invades reticulocytes, as does the canine pathogen B. gibsoni, we infected the susceptible inbred mouse strains C.B-17.scid and DBA/2 with a clinical isolate of B. microti. Staining of fixed permeabilized red blood cells with 4',6'-diamidino-2-phenylindole or YOYO-1, a sensitive nucleic acid stain, revealed parasite nuclei as large bright dots. Flow cytometric analysis indicated that parasite DNA is primarily found in mature erythrocytes that expressed Babesia antigens but not the transferrin receptor CD71. In contrast, CD71-positive reticulocytes rarely contained Babesia nuclei and failed to express Babesia antigens. Accordingly, the frequency of YOYO-1-positive, CD71-negative cells strongly correlated with parasitemia, defined as the frequency of infected red blood cells assessed on Giemsa-stained blood smears. Importantly, the absolute numbers generated by the two techniques were similar. Parasitemia was modest and transient in DBA/2 mice but intense and sustained in C.B-17.scid mice. In both strains, parasitemia preceded reticulocytosis, but reticulocytes remained refractory to B. microti. In immunocompetent C.B-17 mice, reticulocytosis developed early, despite a marginal and short-lived parasitemia. Likewise, an early reticulocytosis developed in resistant BALB/cBy and B10.D2 mice. These studies establish that B. microti has a tropism for mature erythrocytes. Although reticulocytes are rarely infected, the delayed reticulocytosis in susceptible strains may result from parasite or host activities to limit renewal of the mature erythrocyte pool, thereby preventing an overwhelming parasitemia.

Editor: W. A. Petri, Jr.

Present address: Center for Developmental Neurology, Children's Hospital, University of Munich, Lindwurmstr., D-80337 Munich, Germany.