Identification of loci controlling restriction of parasite growth in experimental Taenia crassiceps cysticercosis.
Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a critical role in early protective inflammatory response to infection with T. crassiceps.
Departament of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México.
Ruben
R
Ramirez-Aquino
Irena
I
Radovanovic
Anny
A
Fortin
Edda
E
Sciutto-Conde
Gladis
G
Fragoso-González
Philippe
P
Gros
Irma
I
Aguilar-Delfin
D000818:Animals; D003182:Complement C5 / Q000235:genetics* / Q000276:immunology*; D003433:Crosses, Genetic; D003551:Cysticercosis / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D020641:Polymorphism, Single Nucleotide; D013621:Taenia / Q000276:immunology*
D003182:Complement C5