Brucella melitensisinfection associated with Guillain–Barré syndrome through molecular mimicry of host structures

Abstract

Brucella melitensis is a facultative intracellular bacterium that can survive inside macrophages and the causative agent of brucellosis. In the present study, we found that a lipooligosaccharide of B. melitensis has a GM1 ganglioside-like structure and shows a strong antibody response in mice. The cholera toxin B subunit, which binds to GM1 ganglioside specifically, reacted with the surface of B. melitensis. Immunization with B. melitensis induced the production of anti-GM1 ganglioside antibodies in mice and serum from immunized mice showed a cross-reaction with Guillain-Barré syndrome (GBS)-associated Campylobacter jejuni, but not non-GBS-associated C. jejuni. When B. melitensis was treated with a neuraminidase, antibody responses disappeared. B. melitensis immunization induced the production of anti-GM1 ganglioside antibodies in BALB/c mice but not in C57BL/6 and ddY mice, and for BALB/c mice, immunization with B. melitensis induced much greater production of anti-GM1 ganglioside than GBS-associated C. jejuni. Flaccid limb weakness was observed in B. melitensis immunized mice. These results suggest that B. melitensis is a new etiological agent for GBS and that immunological responses between it and GBS-associated C. jejuni in the mouse model may be different.

Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases

“…In addition, cross-reactivity of antibodies to asialo-GM2 and LOS of a C. jejuni strain from a GBS patient has been demonstrated (26). Interestingly, Watanabe et al (86) reported that an LPS of Brucella melitensis had a GM1 ganglioside-like structure and that B. melitensis is a new etiological agent for GBS. Immunization of mice with B. melitensis induced mice to show flaccid limb weakness and ataxia-like symptoms that may be due to molecular mimicry between B. melitensis LPS containing GM1 ganglioside-like structures and peripheral nerve gangliosides.…”

Frequency of subclinical peripheral neuropathy in cases of untreated brucellosis

“…A study investigating a brucellosis patient with GBS suggested that antibodies against gangliosides were responsible for the pathogenesis of peripheral nerve involvement. This study found that GM1 ganglioside antibodies were produced against molecules similar to gangliosides expressed on the surface of B.melitensis and caused symptoms similar to weakness in extremities and ataxia in rats [18]. As a result, it was proposed that polyradiculopathies related to brucellosis may cause nerve damage due to the antibody response to similarities between GM1 ganglioside molecules in peripheral nerves and Brucella spp.…”

“…As a result, it was proposed that polyradiculopathies related to brucellosis may cause nerve damage due to the antibody response to similarities between GM1 ganglioside molecules in peripheral nerves and Brucella spp. lipooligosaccharides [16,18]. Studies indicate that systemic treatment of brucellosis has caused regression of peripheral neuropathy linked to Brucella spp.…”

Brucella Induced Guillain–Barré Syndrome

“…Furthermore, immunization with B. melitensis, induced the production of anti-GM1 gangeliosides antibodies that resulted in flaccid weakness and ataxia-like symptoms. 11 Cross-reactive immunological responses as a result of this molecular mimicry between Brucella lipooligosaccharide and GM1 gangeliosides may explain the acute axonal polyradiculopathy in Brucella infection.…”