Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes
AuthorPane, JA; Webster, NL; Graham, KL; Holloway, G; Zufferey, C; Coulson, BS
University of Melbourne Author/sHolloway, Gavan; Coulson, Barbara; ZUFFEREY, CHRISTEL; Webster, Nicole; PANE, JESSICA; Graham, Kate
AffiliationMedicine (St Vincent's)
Microbiology and Immunology
Melbourne Graduate School of Education
Research, Innovation and Commercialisation
Document TypeJournal Article
CitationsPane, JA; Webster, NL; Graham, KL; Holloway, G; Zufferey, C; Coulson, BS, Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes, DIABETOLOGIA, 2013, 56 (3), pp. 573 - 582
Access StatusOpen Access
AIMS/HYPOTHESIS: Rotavirus infection in at-risk children correlates with production of serum autoantibodies indicative of type 1 diabetes progression. Oral infection with rhesus monkey rotavirus (RRV) accelerates diabetes onset in mice. This relates to their rotavirus-specific serum antibody titre and local pro-inflammatory cytokine induction without pancreatic infection. Our aim was to further investigate the roles of serum antibodies and viral extra-intestinal spread in diabetes acceleration by rotavirus. METHODS: Rotavirus-specific serum antibody production was detected by ELISA in diabetes-prone mice given either inactivated or low-dose RRV, in relation to their diabetes development. Serum anti-rotavirus antibody titres and infectious virus in lymph nodes were measured in mice given RRV or porcine rotavirus CRW-8. In lymph node cells, rotavirus antigen presence and immune activation were determined by flow cytometry, in conjunction with cytokine mRNA levels. RESULTS: Acceleration of diabetes by RRV required virus replication, which correlated with antibody presence. CRW-8 induced similar specific total immunoglobulin and IgA titres to those induced by RRV, but did not accelerate diabetes. RRV alone elicited specific serum IgG antibodies with a T helper (Th)1 bias, spread to regional lymph nodes and activated antigen-presenting cells at these sites. RRV increased Th1-specific cytokine expression in pancreatic lymph nodes. Diabetes onset was more rapid in the RRV-infected mice with the greater Th1 bias. CONCLUSIONS/INTERPRETATION: Acceleration of murine diabetes by rotavirus is virus strain-specific and associated with virus spread to regional lymph nodes, activation of antigen-presenting cells at these sites and induction of a Th1-dominated antibody and cytokine response.
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