Novel Immunomodulatory Flagellin-Like Protein FlaC in Campylobacter jejuni and Other Campylobacterales

• DOI: 10.1128/msphere.00028-15
• Publication Date: 2015-11-30T13:03:44Z
• Authors: Eugenia Faber; Eugenia Gripp; Sven Maurischat; Bernd Kaspers; Karsten Tedin; Sarah Menz; Aleksandra Zuraw; Olivia Kershaw; Ines Yang; Silke Rautenschlein; Christine Josenhans
• Keywords: TLR5; Flagellin

The human diarrheal pathogens Campylobacter jejuni and coli interfere with host innate immune signaling by different means, their flagellins, FlaA FlaB, have a low intrinsic property to activate the receptor Toll-like 5 (TLR5). We investigated here hypothesis that unusual secreted, flagellin-like molecule FlaC present in C. jejuni, coli, other Campylobacterales might cells via TLR5 interact TLR5. shows striking sequence identity its D1 domains TLR5-activating flagellins of bacteria, such as Salmonella, but not nonstimulating flagellins. overexpressed purified tested immunostimulatory properties on chicken origin. Treatment highly resulted p38 activation. directly interacted Preincubation decreased responsiveness macrophage-like toward bacterial TLR4 agonist lipopolysaccharide (LPS), suggesting mediates cross-tolerance. flaC mutants induced an increase cell responses comparison those wild type, which was suppressed genetic complementation. Supplementing excess likewise reduced cellular response jejuni. In vivo, administration ultrapure led decrease cecal interleukin 1β (IL-1β) expression significant change microbiota chickens. propose spp. evolved novel type secreted effector order specifically modulate responses, for example pattern recognition (PRR) ligands, LPS. IMPORTANCE Flagellins only are important motility major proteins can (TLR5) or receptors. colonizing intestinal tracts species harbor gene coding flagellin, FlaC, is involved possesses chimeric amino acid composed non-TLR5-activating flagellin sequences. activates cytokine cells, promotes cross-tolerance alters microbiota. has tract presence resident may contribute persistence. results also strengthen role flagellar III apparatus functional secretion system proteins.