Decreased nematode clearance & anti-phosphorylcholine specific IgM responses in mannose-binding lectin deficient mice

Ahmed, R and Cadman, E T and Snapper, C M and Lawrence, R A (2018) Decreased nematode clearance & anti-phosphorylcholine specific IgM responses in mannose-binding lectin deficient mice. Immunology & Cell Biology.

[img]
Preview
Text
11845.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial.

Download (1MB) | Preview

Abstract

Brugia malayi is a nematode that causes human lymphatic filariasis. Previously, we showed that mannose binding lectin (MBL) ‐A is necessary for clearance of B. malayi microfilariae in mice and presence of MBL‐A is linked with maximal levels of parasite‐specific IgM. Common human MBL gene polymorphisms result in low MBL expression and lead to recurring bacterial infections. Furthermore, these low‐expressing human MBL polymorphisms result in greatly increased susceptibility to lymphatic filarial infection. Indeed, gain of new filarial infections over a 30‐year period are 10‐fold higher in people with low, compared to high, MBL‐expression phenotypes. Human MBL closely resembles mouse MBL‐C, rather than MBL‐A, therefore we examined the role of mouse MBL‐C in clearance of microfilariae. Absence of MBL‐C alone, or both MBL‐A and ‐C, resulted in delayed clearance of microfilariae and reduced parasite‐specific IgM in mice. There were few profound changes in B cell sub‐populations or in the ability of MBL‐deficient mice to respond to T‐dependent or T‐independent antigens. However, absence of MBL‐A and/or MBL‐C resulted in reduced IgM to phosphorylcholine, a constituent of filarial and bacterial antigens, suggesting that inability to form proficient antibody responses to this moiety leads to lack of microfilarial clearance and overall susceptibility to filariasis.

Actions (Repository Editors)

View Item View Item