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: Tim Carter, Michiko Sumiya, Kerri Reilly, Rubina Ahmed, Peter Sobieszczuk, John A Summerfield, Rachel A Lawrence
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 8 Pg. 5116-23 (Apr 15 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17404294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Helminth
• Complement C3
• Immunoglobulin Isotypes
• Immunoglobulin M
• Mannose-Binding Lectin
• mannose binding protein A

Topics

• Animals
• Antibodies, Helminth (blood)
• Brugia malayi (immunology)
• Complement C3 (physiology)
• Disease Susceptibility
• Filariasis (immunology)
• Immunoglobulin Isotypes (blood)
• Immunoglobulin M (blood)
• Leukocyte Count
• Mannose-Binding Lectin (deficiency, physiology)
• Mice
• Mice, Inbred C57BL