title: The contribution of natural killer complex loci to the development of experimental cerebral malaria.
abstract: BACKGROUND
  The Natural Killer Complex (NKC) is a genetic region of highly linked genes encoding several receptors involved in the control of NK cell function. The NKC is highly polymorphic and allelic variability of various NKC loci has been demonstrated in inbred mice, providing evidence for NKC haplotypes. Using BALB.B6-Cmv1r congenic mice, in which NKC genes from C57BL/6 mice were introduced into the BALB/c background, we have previously shown that the NKC is a genetic determinant of malarial pathogenesis. C57BL/6 alleles are associated with increased disease-susceptibility as BALB.B6-Cmv1r congenic mice had increased cerebral pathology and death rates during P. berghei ANKA infection than cerebral malaria-resistant BALB/c controls.
  
  
  METHODS
  To investigate which regions of the NKC are involved in susceptibility to experimental cerebral malaria (ECM), intra-NKC congenic mice generated by backcrossing recombinant F2 progeny from a (BALB/c x BALB.B6-Cmv1r) F1 intercross to BALB/c mice were infected with P. berghei ANKA.
  
  
  RESULTS
  Our results revealed that C57BL/6 alleles at two locations in the NKC contribute to the development of ECM. The increased severity to severe disease in intra-NKC congenic mice was not associated with higher parasite burdens but correlated with a significantly enhanced systemic IFN-γ response to infection and an increased recruitment of CD8+ T cells to the brain of infected animals.
  
  
  CONCLUSIONS
  Polymorphisms within the NKC modulate malarial pathogenesis and acquired immune responses to infection.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hansen
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ryg-Cornejo
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Ioannidis
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Chris Y
authors.initials: CY
authors.lastname: Chiu
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Ann
authors.initials: A
authors.lastname: Ly
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Catherine Q
authors.initials: CQ
authors.lastname: Nie
authors.affiliation: Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Scalzo
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Douglas, Queensland, Australia.
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
mesh_terms: D000483:Alleles; D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics*; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; C119621:Clec4n protein, mouse; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D007371:Interferon-gamma