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

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...

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Veröffentlicht in:The Journal of infectious diseases 2012-10, Vol.206 (8), p.1233-1241
Hauptverfasser: Liu, Lei, Dai, Jianfeng, Zhao, Yang O., Narasimhan, Sukanya, Yang, Ying, Zhang, Lili, Fikrig, Erol
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container_issue 8
container_start_page 1233
container_title The Journal of infectious diseases
container_volume 206
creator Liu, Lei
Dai, Jianfeng
Zhao, Yang O.
Narasimhan, Sukanya
Yang, Ying
Zhang, Lili
Fikrig, Erol
description 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.
doi_str_mv 10.1093/infdis/jis484
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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.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jis484</identifier><identifier>PMID: 22859824</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Anaplasma phagocytophilum - immunology ; Animals ; Antimicrobial Cationic Peptides - biosynthesis ; Antimicrobial Cationic Peptides - immunology ; BACTERIA ; Biological and medical sciences ; Cell lines ; Disease transmission ; Drosophila ; Electrophoretic Mobility Shift Assay ; Fundamental and applied biological sciences. 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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.</description><subject>Anaplasma phagocytophilum - immunology</subject><subject>Animals</subject><subject>Antimicrobial Cationic Peptides - biosynthesis</subject><subject>Antimicrobial Cationic Peptides - immunology</subject><subject>BACTERIA</subject><subject>Biological and medical sciences</subject><subject>Cell lines</subject><subject>Disease transmission</subject><subject>Drosophila</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Hematopoietic stem cells</subject><subject>Hemolymph</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Ixodes - immunology</subject><subject>Ixodes - microbiology</subject><subject>Janus Kinase 1 - immunology</subject><subject>Major and Brief Reports</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Midgut</subject><subject>Pathogens</subject><subject>Salivary glands</subject><subject>Salivary Glands - immunology</subject><subject>Salivary Glands - microbiology</subject><subject>Signal Transduction</subject><subject>STAT Transcription Factors - immunology</subject><subject>Ticks</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1u1DAURiMEotPCkiXIGyQWhNrxT-INUjSCtlCJCoZ1dOM4Mx6cONgOZV6Bp8YowwhWXnznfr66J8ueEfyGYEkvzdh3JlzuTWAVe5CtCKdlLgShD7MVxkWRk0rKs-w8hD3GmFFRPs7OiqLisirYKvt189N1OqCgYJoteBPQh_pj_mVTb9AdxN09HNBnvU1RTNTGqG-oHqMZjPKuNWDRnZ6iSQ2v0WanvW4PaO3G6J21ZtyiuNOo3uoxItej63mAEV15GGfr1CEalbpgshAGF0x4kj3qwQb99PheZF_fv9usr_PbT1c36_o2VxzzmCvcCtGXoGQLsqww51RTrttCdKXoJIaCVZ2GQlClOk1AKcIFxZ0E1gEVHb3I3i6909wOulNpOw-2mbwZwB8aB6b5PxnNrtm6Hw1lrJKiSgWvjgXefZ91iM1ggtLWwqjdHBqCKyyIKHmZ0HxB07lC8Lo_fUNw88dfs_hrFn-Jf_Hvbif6r7AEvDwCkJTZPh1TpfETJxiRheSJe75w-xCdP-WMlAUvGaO_ARdJsx8</recordid><startdate>20121015</startdate><enddate>20121015</enddate><creator>Liu, Lei</creator><creator>Dai, Jianfeng</creator><creator>Zhao, Yang O.</creator><creator>Narasimhan, Sukanya</creator><creator>Yang, Ying</creator><creator>Zhang, Lili</creator><creator>Fikrig, Erol</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20121015</creationdate><title>Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis</title><author>Liu, Lei ; Dai, Jianfeng ; Zhao, Yang O. ; Narasimhan, Sukanya ; Yang, Ying ; Zhang, Lili ; Fikrig, Erol</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-c0b66f7ac9ba9780553e35eb26d76d90a248dea263ccde1acc15630d9a4da36d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anaplasma phagocytophilum - immunology</topic><topic>Animals</topic><topic>Antimicrobial Cationic Peptides - biosynthesis</topic><topic>Antimicrobial Cationic Peptides - immunology</topic><topic>BACTERIA</topic><topic>Biological and medical sciences</topic><topic>Cell lines</topic><topic>Disease transmission</topic><topic>Drosophila</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Hematopoietic stem cells</topic><topic>Hemolymph</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Ixodes - immunology</topic><topic>Ixodes - microbiology</topic><topic>Janus Kinase 1 - immunology</topic><topic>Major and Brief Reports</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Midgut</topic><topic>Pathogens</topic><topic>Salivary glands</topic><topic>Salivary Glands - immunology</topic><topic>Salivary Glands - microbiology</topic><topic>Signal Transduction</topic><topic>STAT Transcription Factors - immunology</topic><topic>Ticks</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Lei</creatorcontrib><creatorcontrib>Dai, Jianfeng</creatorcontrib><creatorcontrib>Zhao, Yang O.</creatorcontrib><creatorcontrib>Narasimhan, Sukanya</creatorcontrib><creatorcontrib>Yang, Ying</creatorcontrib><creatorcontrib>Zhang, Lili</creatorcontrib><creatorcontrib>Fikrig, Erol</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Lei</au><au>Dai, Jianfeng</au><au>Zhao, Yang O.</au><au>Narasimhan, Sukanya</au><au>Yang, Ying</au><au>Zhang, Lili</au><au>Fikrig, Erol</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2012-10-15</date><risdate>2012</risdate><volume>206</volume><issue>8</issue><spage>1233</spage><epage>1241</epage><pages>1233-1241</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22859824</pmid><doi>10.1093/infdis/jis484</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Anaplasma phagocytophilum - immunology
Animals
Antimicrobial Cationic Peptides - biosynthesis
Antimicrobial Cationic Peptides - immunology
BACTERIA
Biological and medical sciences
Cell lines
Disease transmission
Drosophila
Electrophoretic Mobility Shift Assay
Fundamental and applied biological sciences. Psychology
Gene Expression Profiling
Gene Expression Regulation
Hematopoietic stem cells
Hemolymph
Infections
Infectious diseases
Ixodes - immunology
Ixodes - microbiology
Janus Kinase 1 - immunology
Major and Brief Reports
Medical sciences
Microbiology
Midgut
Pathogens
Salivary glands
Salivary Glands - immunology
Salivary Glands - microbiology
Signal Transduction
STAT Transcription Factors - immunology
Ticks
title Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis
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