HLA class II polymorphism influences onset and severity of pathology in Schistosoma mansoni-infected transgenic mice.
Genetic factors that might influence susceptibility or resistance in naive individuals and early-stage pathology in schistosomiasis are difficult to study in clinical trials, since in areas where the disease is endemic the first contact with the parasite occurs most often at very early ages. Therefore, four strains (DR1.Abeta degrees, DR2.Abeta degrees, DQ8.Abeta degrees, and DQ6.Abeta degrees ) of major histocompatibility complex class II-deficient mice (Abeta degrees ), transgenic for different HLA alleles, have been used to evaluate the potential role of HLA class II polymorphism in the onset of the infection by Schistosoma mansoni. The survival rates and parasitological and immunological parameters after infection were evaluated and compared against the control values obtained with Abeta degrees mice. All four mouse strains used in this study were able to generate a specific immune response against S. mansoni antigens (cytokine production and antibody production). However, only mice expressing DR alleles survived until the chronic stage of the infection and were able to mount protective granulomatous response avoiding hepatic damage, presenting predominant gamma interferon production. In contrast, strains expressing DQ alleles revealed an impairment in generating effective granulomas, resulting in earlier death, which was associated with an impaired hepatic granulomatous response and liquefactic necrosis, reflecting the influence of HLA polymorphism in the establishment of protective response in the early stage of infection.
Angyalosi
G
G
Laboratoire d'Immunopathologie Cellulaire des Maladies Infectieuses, UMR 8527, Institut de Biologie, F-59021 Lille, France. gerhild.angyalosi@ibl.fr
Neveu
R
R
Wolowczuk
I
I
Delanoye
A
A
Herno
J
J
Auriault
C
C
Pancré
V
V
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000235:genetics; D015802:HLA-DR2 Antigen / Q000235:genetics; D008099:Liver / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology*; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019076:Transgenes
D000909:Antibodies, Helminth; D016207:Cytokines; D006683:HLA-DQ Antigens; C063831:HLA-DQ6 antigen; C109756:HLA-DQ8 antigen; D015798:HLA-DR1 Antigen; D015802:HLA-DR2 Antigen