Antialarmin effect of tick saliva during the transmission of Lyme disease.
Tick saliva has potent immunomodulatory properties. In arthropod-borne diseases, this effect is largely used by microorganisms to increase their pathogenicity and to evade host immune responses. We show that in Lyme borreliosis, tick salivary gland extract and a tick saliva protein, Salp15, inhibit in vitro keratinocyte inflammation induced by Borrelia burgdorferi sensu stricto or by the major outer surface lipoprotein of Borrelia, OspC. Chemokines (interleukin-8 [IL-8] and monocyte chemoattractant protein 1 [MCP-1]) and several antimicrobial peptides (defensins, cathelicidin, psoriasin, and RNase 7) were downregulated. Interestingly, antimicrobial peptides (AMPs) transiently inhibited bacterial motility but did not kill the organisms when tested in vitro. We conclude that tick saliva affects the chemotactic properties of chemokines and AMPs on immune cells and has an antialarmin effect on human primary keratinocytes. Alarmins are mediators that mobilize and activate antigen-presenting cells. Inhibition of cutaneous innate immunity and of the migration of immune cells to the site of the tick bite ensures a favorable environment for Borrelia. The bacterium can then multiply locally and, subsequently, disseminate to the target organs, including joints, heart, and the central nervous system.
EA 4438, Physiopathologie et Médecine Translationnelle, Facultés de Médecine et de Pharmacie, Université de Strasbourg, 67000 Strasbourg, France.
Claire
C
Marchal
Frederic
F
Schramm
Aurélie
A
Kern
Benjamin J
BJ
Luft
Xiaohua
X
Yang
Tim J
TJ
Schuijt
Tim
T
Schuijt
Joppe W
JW
Hovius
Joppe
J
Hovius
Benoît
B
Jaulhac
Nathalie
N
Boulanger
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D001096:Arachnid Vectors / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D008193:Lyme Disease / Q000635:transmission*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012463:Saliva / Q000737:chemistry / Q000276:immunology; D012469:Salivary Glands / Q000737:chemistry; D012471:Salivary Proteins and Peptides / Q000276:immunology; D013987:Ticks / Q000502:physiology*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D012333:RNA, Messenger; D012471:Salivary Proteins and Peptides; C464566:Salp15 protein, Ixodes scapularis; D002762:Cholecalciferol; D054804:Cathelicidins