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.
Highlights
Mannose binding lectin is critical for innate recognition and clearance of Brugia malayi, a parasitic nematode that causes the major human tropical disease, lymphatic filariasis 1
To elucidate whether both mannose binding lectin (MBL)-A and MBL-C are efficient at binding microfilarial antigens, we investigated their ability to bind to the control polysaccharide, mannan, as well as to microfilarial and adult extracts
MBL-C was relatively weak at binding microfilarial antigen (Figure S1e) while MBL-C bound to adult Brugia extract effectively (Figure S1f), suggesting that mannose binding lectin-A (MBL-A) may bind to B. malayi microfilarial glycans more efficiently than MBL-C
Summary
Mannose binding lectin is critical for innate recognition and clearance of Brugia malayi, a parasitic nematode that causes the major human tropical disease, lymphatic filariasis 1. We previously revealed an intriguing connection between the presence of mannose binding lectin-A (MBL-A), removal of B. malayi microfilariae and induction of parasite-specific IgM antibody 1. The necessity of just a single pattern recognition receptor (PRR) - glycan interaction for the induction of protective immunity during a helminth infection is a novelty to our knowledge. Induction of T helper 2 (Th2) responses to another helminth, Schistosoma mansoni, is glycan-mediated, and while protective immunity to schistosome infection has yet to be directly linked to PRR recognition of glycan structures, recognition of glycan structures by antibody is capable of killing schistosomes as well as other helminths [4,5,6]. Despite the well-known importance of anti-polysaccharide responses in bacterial vaccines, induction of anti-glycan immunity is poorly understood
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