title: Mannose-binding lectin A-deficient mice have abrogated antigen-specific IgM responses and increased susceptibility to a nematode infection.
abstract: To investigate the role of mannose-binding lectin-A (MBL-A) in protection against infectious disease, MBL-A(-/-)-deficient mice were generated. Using a well-characterized mouse model of human filarial nematode infection, nematode survival and protective immune responses were tested in vivo. Blood-borne Brugia malayi microfilariae survived for significantly longer time periods in MBL-A(-/-) than in wild-type (WT) mice. However, no differences in either splenic cytokine responses or induction of leukocytes in the blood were observed. A profound abrogation of Ag-specific IgM levels was measured in B. malayi-infected MBL-A(-/-) mice, and some IgG isotypes were higher than those observed in WT animals. To establish whether there was a defect in Ab responses per se in MBL-A(-/-) mice or the effect was specific to filarial infection, we immunized these mice with OVA or a carbohydrate-free protein. Significantly, Ag-specific IgM responses were defective to both of these Ags, and Ag-specific IgG responses were largely unaffected. Furthermore, in naive mice, total IgM levels did not differ between MBL-A(-/-) and WT mice. This article describes the first demonstration that MBL-A may function independently of MBL-C and suggests that MBL-A, like other C-type lectins and members of the complement cascade, is intimately involved in the priming of the humoral Ab response.
authors.affiliation: Department of Medicine, Imperial College London, St. Mary's Campus, London, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Carter
authors.forename: Michiko
authors.initials: M
authors.lastname: Sumiya
authors.forename: Kerri
authors.initials: K
authors.lastname: Reilly
authors.forename: Rubina
authors.initials: R
authors.lastname: Ahmed
authors.forename: Peter
authors.initials: P
authors.lastname: Sobieszczuk
authors.forename: John A
authors.initials: JA
authors.lastname: Summerfield
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D017178:Brugia malayi / Q000276:immunology*; D003176:Complement C3 / Q000502:physiology; D004198:Disease Susceptibility; D005368:Filariasis / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood*; D007958:Leukocyte Count; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000909:Antibodies, Helminth; D003176:Complement C3; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D037601:Mannose-Binding Lectin; C069858:mannose binding protein A