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 |
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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. |
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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. 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</subject><ispartof>The Journal of infectious diseases, 2012-10, Vol.206 (8), p.1233-1241</ispartof><rights>Copyright © 2012 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>2015 INIST-CNRS</rights><rights>The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-c0b66f7ac9ba9780553e35eb26d76d90a248dea263ccde1acc15630d9a4da36d3</citedby><cites>FETCH-LOGICAL-c505t-c0b66f7ac9ba9780553e35eb26d76d90a248dea263ccde1acc15630d9a4da36d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41725744$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41725744$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,27903,27904,57996,58229</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26419295$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22859824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><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.</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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