Increased exposure to Plasmodium chabaudi antigens sustains cross-reactivity and avidity of antibodies binding Nippostrongylus brasiliensis: dissecting cross-phylum cross-reactivity in a rodent model

被引:4
|
作者
Fairlie-Clarke, Karen J. [1 ]
Hansen, Christina [2 ]
Allen, Judith E. [1 ]
Graham, Andrea L. [1 ,2 ]
机构
[1] Univ Edinburgh, Inst Evolut Immunol & Infect Res, Sch Biol Sci, Edinburgh, Midlothian, Scotland
[2] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA
基金
英国生物技术与生命科学研究理事会;
关键词
antibody; avidity; cross-reactivity; parasite dose; co-infection; malaria; nematode; antigen exposure; B-CELL RESPONSES; SCHISTOSOMA-MANSONI; AFFINITY MATURATION; INFECTION; MALARIA; MICE; SELECTION; IMMUNITY; HYPERMUTATION; SPECIFICITY;
D O I
10.1017/S0031182015001390
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Mounting an antibody response capable of discriminating amongst and appropriately targeting different parasites is crucial in host defence. However, cross-reactive antibodies that recognize (bind to) multiple parasite species are well documented. We aimed to determine if a higher inoculating dose of one species, and thus exposure to larger amounts of antigen over a longer period of time, would fine-tune responses to that species and reduce cross-reactivity. Using the Plasmodium chabaudi chabaudi (Pcc)-Nippostrongylus brasiliensis (Nb) co-infection model in BALB/c mice, in which we previously documented cross-reactive antibodies, we manipulated the inoculating dose of Pcc across 4 orders of magnitude. We investigated antigen-specific and cross-reactive antibody responses against crude and defined recombinant antigens by enzyme linked immunosorbent assay, Western blot and antibody depletion assays. Contrary to our hypothesis that increasing exposure to Pcc would reduce cross-reactivity to Nb, we found evidence for increased avidity of a subpopulation of antibodies that recognized shared antigens. Western blot indicated proteins of apparent monomer molecular mass 28 and 98 kDa in both Nb and Pcc antigen preparations and also an Nb protein of similar size to recombinant Pcc antigen, merozoite surface protein-1(19). The implications of antibodies binding antigen from such phylogenetically distinct parasites are discussed.
引用
收藏
页码:1703 / 1714
页数:12
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