Role of Campylobacter jejuni infection in the pathogenesis of Guillain-Barré syndrome: an update

Abstract

Our current knowledge on Campylobacter jejuni infections in humans has progressively increased over the past few decades. Infection with C. jejuni is the most common cause of bacterial gastroenteritis, sometimes surpassing other infections due to Salmonella, Shigella, and Escherichia coli. Most infections are acquired due to consumption of raw or undercooked poultry, unpasteurized milk, and contaminated water. After developing the diagnostic methods to detect C. jejuni, the possibility to identify the association of its infection with new diseases has been increased. After the successful isolation of C. jejuni, reports have been published citing the occurrence of GBS following C. jejuni infection. Thus, C. jejuni is now considered as a major triggering agent of GBS. Molecular mimicry between sialylated lipooligosaccharide structures on the cell envelope of these bacteria and ganglioside epitopes on the human nerves that generates cross-reactive immune response results in autoimmune-driven nerve damage. Though C. jejuni is associated with several pathologic forms of GBS, axonal subtypes following C. jejuni infection may be more severe. Ample amount of existing data covers a large spectrum of GBS; however, the studies on C. jejuni-associated GBS are still inconclusive. Therefore, this review provides an update on the C. jejuni infections engaged in the pathogenesis of GBS.

Figure 1

Sources and transmission of Campylobacter jejuni. Chicken is a natural reservoir of the C. jejuni where it colonizes in the mucosal layer of the gastrointestinal tract and can transfer between chickens through the faecal-oral route. C. jejuni can contaminate water and probably form an association with protozoans. Humans who encounter contaminated water, consume undercooked poultry, and unpasteurized milk get infected. The bacterium resides in the epithelial layer of the human gastrointestinal route and causes mainly inflammation and diarrhea. Sometimes antibodies produced against the bacterium mimic with the host nerve gangliosides resulting in demyelination and axonal degeneration of peripheral nerves that causes Guillain-Barré syndrome.

Figure 2

Different laboratory methods for the detection of Campylobacter jejuni in patients with Guillain-Barré syndrome.

Figure 3

Origin and contribution of antiganglioside antibodies and C. jejuni infection to Guillain-Barré syndrome pathogenesis. A bacterial cross-reactive antigen recognized by macrophages and T cells that help B cells to produce antiganglioside antibodies, which penetrate blood-nerve barrier and activate complement. These antibodies bind with specific nerve gangliosides and C. jejuni antigen as well. Activated endoneurial macrophages release cytokine and free radicals (nitric oxide), invade compact myelin, periaxonal space, and sometimes block nerve conduction or cause axonal degeneration. Activated T cells release proinflammatory cytokines, fix complement, damage Schwann cell, and ultimately produce dissolution of myelin.