TY - JOUR
T1 - Innate Immunity to Campylobacter jejuni in Guillain-Barré Syndrome
AU - Huizinga, Ruth
AU - Van Den Berg, Bianca
AU - Van Rijs, Wouter
AU - Tio-Gillen, Anne P.
AU - Fokkink, Willem Jan R
AU - Bakker-Jonges, Liesbeth E.
AU - Geleijns, Karin
AU - Samsom, Janneke N.
AU - Van Doorn, Pieter A.
AU - Laman, Jon D.
AU - Jacobs, Bart C.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Objective: Guillain-Barré syndrome (GBS) is a postinfectious neuropathy most frequently caused by Campylobacter jejuni. Lipo-oligosaccharides (LOS), expressed by C. jejuni induce antibodies that cross-react with self-glycolipids in peripheral nerves, causing neuropathy. Less than 1 in 1,000 persons infected with C. jejuni develop GBS, and the factors that determine GBS susceptibility are poorly understood. We hypothesized that these persons have a high intrinsic dendritic cell (DC) response to C. jejuni LOS through Toll-like receptor 4 (TLR4) activation. Methods: Intrinsic DC responsiveness to C. jejuni LOS was investigated first in 20 healthy controls at three time points with a 3-month interval, and second in patients, who previously developed GBS after a C. jejuni infection (n = 27) and controls (n = 26). Results: The DC response to C. jejuni LOS was highly variable between, but not within, healthy individuals, suggesting that intrinsic factors determine the magnitude of TLR4-mediated innate response. High responsiveness to C. jejuni LOS by former GBS patients was evidenced by increased expression of CD38 and CD40. Frequency of CD38, CD40 and type I interferon high responders was significantly increased in the GBS group. Interpretation: These results suggest that a strong response to TLR4 stimulation is a critical host condition for the development of GBS after an infection with C. jejuni.
AB - Objective: Guillain-Barré syndrome (GBS) is a postinfectious neuropathy most frequently caused by Campylobacter jejuni. Lipo-oligosaccharides (LOS), expressed by C. jejuni induce antibodies that cross-react with self-glycolipids in peripheral nerves, causing neuropathy. Less than 1 in 1,000 persons infected with C. jejuni develop GBS, and the factors that determine GBS susceptibility are poorly understood. We hypothesized that these persons have a high intrinsic dendritic cell (DC) response to C. jejuni LOS through Toll-like receptor 4 (TLR4) activation. Methods: Intrinsic DC responsiveness to C. jejuni LOS was investigated first in 20 healthy controls at three time points with a 3-month interval, and second in patients, who previously developed GBS after a C. jejuni infection (n = 27) and controls (n = 26). Results: The DC response to C. jejuni LOS was highly variable between, but not within, healthy individuals, suggesting that intrinsic factors determine the magnitude of TLR4-mediated innate response. High responsiveness to C. jejuni LOS by former GBS patients was evidenced by increased expression of CD38 and CD40. Frequency of CD38, CD40 and type I interferon high responders was significantly increased in the GBS group. Interpretation: These results suggest that a strong response to TLR4 stimulation is a critical host condition for the development of GBS after an infection with C. jejuni.
UR - http://www.scopus.com/inward/record.url?scp=84939650436&partnerID=8YFLogxK
U2 - 10.1002/ana.24442
DO - 10.1002/ana.24442
M3 - Article
AN - SCOPUS:84939650436
SN - 0364-5134
VL - 78
SP - 343
EP - 354
JO - Annals of Neurology
JF - Annals of Neurology
IS - 3
ER -