title: Ixodes scapularis JAK-STAT pathway regulates tick antimicrobial peptides, thereby controlling the agent of human granulocytic anaplasmosis.
abstract: Ixodes scapularis transmits the agent of human granulocytic anaplasmosis, among other pathogens. The mechanisms used by the tick to control Anaplasma phagocytophilum are not known. We demonstrate that the I. scapularis Janus kinase (JAK)-signaling transducer activator of transcription (STAT) pathway plays a critical role in A. phagocytophilum infection of ticks. The A. phagocytophilum burden increases in salivary glands and hemolymph when the JAK-STAT pathway is suppressed by RNA interference. The JAK-STAT pathway exerts its anti-Anaplasma activity presumably through STAT-regulated effectors. A salivary gland gene family encoding 5.3-kDa antimicrobial peptides is highly induced upon A. phagocytophilum infection of tick salivary glands. Gene expression and electrophoretic mobility shift assays showed that the 5.3-kDa antimicrobial peptide-encoding genes are regulated by tick STAT. Silencing of these genes increased A. phagocytophilum infection of tick salivary glands and transmission to mammalian host. These data suggest that the JAK-STAT signaling pathway plays a key role in controlling A. phagocytophilum infection in ticks by regulating the expression of antimicrobial peptides.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Dai
authors.forename: Yang O
authors.initials: YO
authors.lastname: Zhao
authors.forename: Sukanya
authors.initials: S
authors.lastname: Narasimhan
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D041081:Anaplasma phagocytophilum / Q000276:immunology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000276:immunology*; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018884:Ixodes / Q000276:immunology / Q000382:microbiology*; D053613:Janus Kinase 1 / Q000276:immunology*; D050791:STAT Transcription Factors / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology / Q000382:microbiology; D015398:Signal Transduction
chemical_list: D023181:Antimicrobial Cationic Peptides; D050791:STAT Transcription Factors; D053613:Janus Kinase 1