Ixodes Scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2012 Aug 4

PMID 22859824

Citations 52

Authors

Lei Liu

Jianfeng Dai

Yang O Zhao

Sukanya Narasimhan

Ying Yang

Lili Zhang

Erol Fikrig

Affiliations

Soon will be listed here.

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.

Citing Articles

Investigation of genes expression of the JAK/STAT signalling pathway and AMPs in the presence of Borrelia spirochetes in Ixodes ricinus.

Szczotko M, Antunes S, Domingos A, Dmitryjuk M Sci Rep. 2025; 15(1):2869.

PMID: 39843584 PMC: 11754740. DOI: 10.1038/s41598-025-87506-6.

The Tick Microbiome: The "Other Bacterial Players" in Tick Biocontrol.

Maldonado-Ruiz P Microorganisms. 2025; 12(12.

PMID: 39770654 PMC: 11676601. DOI: 10.3390/microorganisms12122451.

Hard Ticks as Vectors: The Emerging Threat of Tick-Borne Diseases in India.

Perumalsamy N, Sharma R, Subramanian M, Nagarajan S Pathogens. 2024; 13(7).

PMID: 39057783 PMC: 11279560. DOI: 10.3390/pathogens13070556.

Potential mechanisms implied in tick infection by arboviruses and their transmission to vertebrate hosts.

Yuan C, Xu Q, Ning Y, Xia Q Integr Zool. 2024; 20(2):315-330.

PMID: 39016029 PMC: 11897945. DOI: 10.1111/1749-4877.12875.

Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2.

Gracias S, Chazal M, Decombe A, Unterfinger Y, Sogues A, Pruvost L EMBO Rep. 2023; 24(12):e57424.

PMID: 37860832 PMC: 10702846. DOI: 10.15252/embr.202357424.

References

Hynes W, Ceraul S, Todd S, Seguin K, Sonenshine D . A defensin-like gene expressed in the black-legged tick, Ixodes scapularis. Med Vet Entomol. 2005; 19(4):339-44. DOI: 10.1111/j.1365-2915.2005.00579.x. View

Boutros M, Agaisse H, Perrimon N . Sequential activation of signaling pathways during innate immune responses in Drosophila. Dev Cell. 2002; 3(5):711-22. DOI: 10.1016/s1534-5807(02)00325-8. View

Telford 3rd S, Armstrong P, Katavolos P, Foppa I, Garcia A, Wilson M . A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini. Emerg Infect Dis. 1997; 3(2):165-70. PMC: 2627606. DOI: 10.3201/eid0302.970209. View

Agaisse H, Perrimon N . The roles of JAK/STAT signaling in Drosophila immune responses. Immunol Rev. 2004; 198:72-82. DOI: 10.1111/j.0105-2896.2004.0133.x. View

Liu L, Narasimhan S, Dai J, Zhang L, Cheng G, Fikrig E . Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands. EMBO Rep. 2011; 12(11):1196-203. PMC: 3207102. DOI: 10.1038/embor.2011.177. View

Thomas V, Fikrig E . Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection. Cell Microbiol. 2007; 9(7):1730-7. DOI: 10.1111/j.1462-5822.2007.00908.x. View

Lemaitre B, Nicolas E, Michaut L, Reichhart J, Hoffmann J . The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996; 86(6):973-83. DOI: 10.1016/s0092-8674(00)80172-5. View

Dai J, Narasimhan S, Zhang L, Liu L, Wang P, Fikrig E . Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent. PLoS Pathog. 2010; 6(11):e1001205. PMC: 2991271. DOI: 10.1371/journal.ppat.1001205. View

Hodzic E, Ijdo J, Feng S, Katavolos P, Sun W, Maretzki C . Granulocytic ehrlichiosis in the laboratory mouse. J Infect Dis. 1998; 177(3):737-45. DOI: 10.1086/514236. View

10.

Hoffmann J . The immune response of Drosophila. Nature. 2003; 426(6962):33-8. DOI: 10.1038/nature02021. View

11.

BURGDORFER W, Barbour A, Hayes S, Benach J, GRUNWALDT E, Davis J . Lyme disease-a tick-borne spirochetosis?. Science. 1982; 216(4552):1317-9. DOI: 10.1126/science.7043737. View

12.

Kopacek P, Hajdusek O, Buresova V, Daffre S . Tick innate immunity. Adv Exp Med Biol. 2011; 708:137-62. View

13.

Gupta L, Molina-Cruz A, Kumar S, Rodrigues J, Dixit R, Zamora R . The STAT pathway mediates late-phase immunity against Plasmodium in the mosquito Anopheles gambiae. Cell Host Microbe. 2009; 5(5):498-507. PMC: 2701194. DOI: 10.1016/j.chom.2009.04.003. View

14.

Ribeiro J, Alarcon-Chaidez F, Francischetti I, Mans B, Mather T, Valenzuela J . An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks. Insect Biochem Mol Biol. 2006; 36(2):111-29. DOI: 10.1016/j.ibmb.2005.11.005. View

15.

De Gregorio E, Spellman P, Tzou P, Rubin G, Lemaitre B . The Toll and Imd pathways are the major regulators of the immune response in Drosophila. EMBO J. 2002; 21(11):2568-79. PMC: 126042. DOI: 10.1093/emboj/21.11.2568. View

16.

Pichu S, Ribeiro J, Mather T . Purification and characterization of a novel salivary antimicrobial peptide from the tick, Ixodes scapularis. Biochem Biophys Res Commun. 2009; 390(3):511-5. PMC: 3740409. DOI: 10.1016/j.bbrc.2009.09.127. View

17.

Kaneko T, Silverman N . Bacterial recognition and signalling by the Drosophila IMD pathway. Cell Microbiol. 2005; 7(4):461-9. DOI: 10.1111/j.1462-5822.2005.00504.x. View

18.

Lawson D, Arensburger P, Atkinson P, Besansky N, Bruggner R, Butler R . VectorBase: a data resource for invertebrate vector genomics. Nucleic Acids Res. 2008; 37(Database issue):D583-7. PMC: 2686483. DOI: 10.1093/nar/gkn857. View

19.

Thomas V, Samanta S, Wu C, Berliner N, Fikrig E . Anaplasma phagocytophilum modulates gp91phox gene expression through altered interferon regulatory factor 1 and PU.1 levels and binding of CCAAT displacement protein. Infect Immun. 2004; 73(1):208-18. PMC: 538944. DOI: 10.1128/IAI.73.1.208-218.2005. View

20.

Reddy S, Alcantara O, Boldt D . Analysis of DNA binding proteins associated with hemin-induced transcriptional inhibition. The hemin response element binding protein is a heterogeneous complex that includes the Ku protein. Blood. 1998; 91(5):1793-801. View