title: Age-associated decline in resistance to Babesia microti is genetically determined.
abstract: BACKGROUND
  Although infection by the protozoan Babesia microti is rarely symptomatic in immunocompetent young people, healthy individuals aged >50 years may experience life-threatening disease. To determine the basis for this age relationship, we developed a mouse model of babesiosis using a novel clinical isolate of B. microti.
  
  
  METHODS
  Mice were infected at 2, 6, 12, or 18 months. Parasitemia was monitored on Giemsa-stained blood smears or by flow cytometry.
  
  
  RESULTS
  In DBA/2 mice, early and persistent parasitemias increased with age at infection. BALB/c and C57BL/6 mice were resistant, regardless of age, which indicates that allelic variation determines resistance to B. microti. Unlike immunocompetent mice, SCID mice, which retain an innate immune system but lack the lymphocytes needed for adaptive immunity, developed high and persistent levels of parasitemia that were markedly reduced by transfer of naive BALB/c or DBA/2 splenocytes. BALB/c cells reduced the persistent parasitemia to a greater extent than did age-matched DBA/2 cells. Of importance, there was an age-associated loss of protection by cells of both strains.
  
  
  CONCLUSIONS
  The resistance to B. microti infection conferred by the adaptive immune system is genetically determined and associated with age. We postulate that there are age-related differences in the expression of alleles critical for adaptive immunity to B. microti.
authors.affiliation: Division of Infectious Diseases, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Edouard
authors.initials: E
authors.lastname: Vannier
authors.forename: Ingo
authors.initials: I
authors.lastname: Borggraefe
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Telford
authors.forename: Sanjay
authors.initials: S
authors.lastname: Menon
authors.forename: Timothy
authors.initials: T
authors.lastname: Brauns
authors.forename: Andrew
authors.initials: A
authors.lastname: Spielman
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gelfand
authors.forename: Henry H
authors.initials: HH
authors.lastname: Wortis
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D041001:Babesia microti / Q000472:pathogenicity*; D001404:Babesiosis / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D018512:Parasitemia / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology