Robert G. Andrews; Yixin Lin; Limin Lee; Lisa H. Athey; Wei Wang; Xiaobo Chen
Abstract
Guillain-Barré syndrome (GBS) is an acute inflammatory disease of the peripheral nervous system characterized by progressive, symmetrical, and ultimately areflexic weakness due to demyelination of spinal and cranial nerves. The paralysis usually occurs a few days or weeks after the onset of preceding symptoms. Up to 90% of patients diagnosed with GBS experience an acute infectious episode, with Campylobacter jejuni enteritis being one of the most documented associations. In several cases, prior infections with Cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, Mycobacterium tuberculosis, or Zika virus have also been reported. Rarely, GBS may occur after trauma, vaccination (e.g., against rabies and influenza), or as a consequence of surgery. Infection or damage to peripheral neurons leads to abnormal presentation of self-antigens or myelin antigens (if there is damage of myelinated fibers), with the consequent activation of T- and B-lymphocytes. The former migrate to the peripheral nerves and attack them, whereas the latter produce autoreactive antibodies targeting peripheral nerve antigens, mostly following the molecular mimicry mechanism. It is still debated whether the neurotoxicity incurred by the rise of cytokines and chemokines and the aberrant immune attack are enough to explain the widespread demyelination and axonal degeneration observed in GBS. Macrophages are typically the first immune cells to infiltrate injured nerves, being crucial to the phenomena of Wallerian degeneration and regeneration. However, they have been pointed to as key participants in different demyelinating diseases of the central and peripheral nervous systems. Macrophages can adopt different phenotypes ranging from the cytotoxic M1-class, which promote demyelination, inflammation, and apoptosis, to the neuroprotective M2-class, which support remyelination and recovery. This review aims to present the current knowledge about the pro-inflammatory and anti-inflammatory role of macrophages in peripheral neuropathies and discuss the potential contribution of macrophages to the outcome of GBS, thus providing possible avenues for future research. Understanding the pathophysiological mechanisms involved in GBS is essential for developing protective or immunomodulatory therapeutic strategies.
Keywords: Guillain-Barré syndrome; macrophages; Acute motor axonal neuropathy; Campylobacter jejuni
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