Boosted Rat Natural Xenoantibodies Cross-React with <b><i>Enterococcus faecalis</i></b> by Targeting Melibiose and <smlcap>L</smlcap>-Rhamnose

Abstract

Natural antibodies include a subset described as xenoantibodies considered to be directed at microorganisms and also cross-react with antigens of unrelated species. In this study, we generated T-cell-independent (TI) and T-cell-dependent (TD) xenoantibodies in Lewis rats with hamster and pig blood injections. TI anti-hamster and anti-pig IgM and IgG xenoantibodies cross-reacted with Enterococcus faecalis but not with Escherichia coli isolated from the blood of Lewis rats after cecal ligation and puncture (CLP). TI anti-pig IgM xenoantibodies also showed some reactivity with two human blood isolates of E. faecalis. In contrast, TD xenoantibodies did not show any reactivity with rat or human bacteria. TI and TD anti-hamster and anti-pig IgM and IgG xenoantibodies showed cross-reactivity with lymphocytes and endothelial cells from species distinct to that used for immunization. Glycan array analysis and inhibition assays identified antibodies against melibiose and <smlcap>L</smlcap>-rhamnose as mediators of anti-hamster and anti-porcine xenoantibody cross-reactivity with E. faecalis. A rise in TI anti-hamster and anti-pig xenoantibodies was accompanied by decreased survival of Lewis rats in a low-severity sepsis model of CLP. Therefore, TI xenoantibodies in the rat include anti-carbohydrate antibodies reactive to bacteria of endogenous flora. Enhancement of these antibodies may result in more severe infectious diseases caused by these microorganisms.

Immunological Memory in Innate Immunity

“…Nonspecific effects of lipopolysaccharides on antiviral type I interferons are involved in these effects. In addition to effects mediated through cellular mechanisms, generation of natural xenoantibodies also induces nonspecific effects during infection, as shown by Perez-Cruz et al [7]. Finally, nonspecific adaptive characteristics of innate immunity are shown to occur and to be sustained for at least 1 year after vaccination in humans.…”

Divergence of the Response Induced by Xenogenic Immunization in the Sepsis Survival of Rats

“…This condition predicted later risk for enteric peritonitis in peritoneal dialysis patients and mortality in both peritoneal dialysis and hemodialysis patients [ 11 ]. In addition, we have recently shown that boosted TI xenoantibodies in rats by exposure to hamster or pig antigens cross-react to Enterococcus faecalis by targeting melibiose and L-rhamnose carbohydrates [ 12 ]. This circumstance was associated with reduced survival of these animals after CLP, which was not observed with the generation of IgG antibodies.…”