Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7
Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechani...
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| Veröffentlicht in: | PLoS pathogens 2010-03, Vol.6 (3), p.e1000813-e1000813 |
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| creator | Phillips, Rebecca Svensson, Mattias Aziz, Naveed Maroof, Asher Brown, Najmeeyah Beattie, Lynette Signoret, Nathalie Kaye, Paul M |
| description | Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells. |
| doi_str_mv | 10.1371/journal.ppat.1000813 |
| format | Article |
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Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Phillips R, Svensson M, Aziz N, Maroof A, Brown N, et al. (2010) Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7. 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This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells.</description><subject>Animals</subject><subject>Gene Expression - immunology</subject><subject>Genetic aspects</subject><subject>Host-bacteria relationships</subject><subject>Immunology/Immunity to Infections</subject><subject>Immunology/Innate Immunity</subject><subject>Infectious Diseases/Neglected Tropical Diseases</subject><subject>Interferon Regulatory Factor-7 - genetics</subject><subject>Interferon Regulatory Factor-7 - immunology</subject><subject>Interferon Regulatory Factor-7 - metabolism</subject><subject>Interferon-alpha - immunology</subject><subject>Interferon-alpha - metabolism</subject><subject>Interferon-gamma - immunology</subject><subject>Interferon-gamma - metabolism</subject><subject>Leishmania</subject><subject>Leishmania donovani - immunology</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis, Visceral - immunology</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - immunology</subject><subject>Macrophages - parasitology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiology/Parasitology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Phagosomes - immunology</subject><subject>Physiological aspects</subject><subject>RNA, Small Interfering</subject><subject>Sinuses</subject><subject>Spleen - immunology</subject><subject>Spleen - parasitology</subject><subject>Streptococcus infections</subject><subject>Viral infections</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqVkk1v1DAQhiMEoqXwDxBE4oA4ZPFX7ORSqaoorLQCqcDZOPYk623WTuOkUH49DptWjcQF-eDR-HlfjWcmSV5itMJU4Pc7P_ZOtauuU8MKI4QKTB8lxzjPaSaoYI8fxEfJsxB2CDFMMX-aHBFEEeIIHSc_1s6pAdIr27bWNamv0w3YsN0rZ1VqvPM3MUqr23SvdO-7rWogTNSwhTR0LTir41Pf2FhL-ts7SHu4Hm0fqfXlRSaeJ09q1QZ4Md8nyfeLD9_OP2WbLx_X52ebTAvKh6wuOSuqCjBXhalqWlc65wZj4EjnNSsNGMVLjJXJERhSU54Dw6I0BakFKww9SV4ffLvWBzk3J0hMihIJVBQ0EusDYbzaya63sexb6ZWVfxO-b6TqB6tbkBoqqqjWtGKC6ajOGXDOy8IgzFSJold28Ao_oRurhducuooRyDwnTOSRP52rG6s9GA1u6FW7kC1fnN3Kxt9IUsTxocng7WzQ--sRwiD3NmhoW-XAj0EKShkicbyRfHMgGxV_Yl3to6GeaHlGCCWE52RqxuofVDwG9lbHMdY25heCdwtBZAb4NTRqDEGuv17-B_t5ybIDG7crhB7q-6ZgJKdFv5ulnBZdzoseZa8eNvRedLfZ9A_EVfo7</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Phillips, Rebecca</creator><creator>Svensson, Mattias</creator><creator>Aziz, Naveed</creator><creator>Maroof, Asher</creator><creator>Brown, Najmeeyah</creator><creator>Beattie, Lynette</creator><creator>Signoret, Nathalie</creator><creator>Kaye, Paul M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20100301</creationdate><title>Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7</title><author>Phillips, Rebecca ; Svensson, Mattias ; Aziz, Naveed ; Maroof, Asher ; Brown, Najmeeyah ; Beattie, Lynette ; Signoret, Nathalie ; Kaye, Paul M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c736t-f9648bbe16a8dbf3fbc56d11e60c5f49deda6911ad50ed2f365e4179d82f748d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Gene Expression - immunology</topic><topic>Genetic aspects</topic><topic>Host-bacteria relationships</topic><topic>Immunology/Immunity to Infections</topic><topic>Immunology/Innate Immunity</topic><topic>Infectious Diseases/Neglected Tropical Diseases</topic><topic>Interferon Regulatory Factor-7 - genetics</topic><topic>Interferon Regulatory Factor-7 - immunology</topic><topic>Interferon Regulatory Factor-7 - metabolism</topic><topic>Interferon-alpha - immunology</topic><topic>Interferon-alpha - metabolism</topic><topic>Interferon-gamma - immunology</topic><topic>Interferon-gamma - metabolism</topic><topic>Leishmania</topic><topic>Leishmania donovani - immunology</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis, Visceral - immunology</topic><topic>Macrophages</topic><topic>Macrophages - cytology</topic><topic>Macrophages - immunology</topic><topic>Macrophages - parasitology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiology/Parasitology</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Phagosomes - immunology</topic><topic>Physiological aspects</topic><topic>RNA, Small Interfering</topic><topic>Sinuses</topic><topic>Spleen - immunology</topic><topic>Spleen - parasitology</topic><topic>Streptococcus infections</topic><topic>Viral infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Phillips, Rebecca</creatorcontrib><creatorcontrib>Svensson, Mattias</creatorcontrib><creatorcontrib>Aziz, Naveed</creatorcontrib><creatorcontrib>Maroof, Asher</creatorcontrib><creatorcontrib>Brown, Najmeeyah</creatorcontrib><creatorcontrib>Beattie, Lynette</creatorcontrib><creatorcontrib>Signoret, Nathalie</creatorcontrib><creatorcontrib>Kaye, Paul M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Phillips, Rebecca</au><au>Svensson, Mattias</au><au>Aziz, Naveed</au><au>Maroof, Asher</au><au>Brown, Najmeeyah</au><au>Beattie, Lynette</au><au>Signoret, Nathalie</au><au>Kaye, Paul M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>6</volume><issue>3</issue><spage>e1000813</spage><epage>e1000813</epage><pages>e1000813-e1000813</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20300600</pmid><doi>10.1371/journal.ppat.1000813</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Animals Gene Expression - immunology Genetic aspects Host-bacteria relationships Immunology/Immunity to Infections Immunology/Innate Immunity Infectious Diseases/Neglected Tropical Diseases Interferon Regulatory Factor-7 - genetics Interferon Regulatory Factor-7 - immunology Interferon Regulatory Factor-7 - metabolism Interferon-alpha - immunology Interferon-alpha - metabolism Interferon-gamma - immunology Interferon-gamma - metabolism Leishmania Leishmania donovani - immunology Leishmaniasis Leishmaniasis, Visceral - immunology Macrophages Macrophages - cytology Macrophages - immunology Macrophages - parasitology Mice Mice, Inbred C57BL Microbiology/Parasitology Nitric oxide Nitric Oxide - metabolism Phagosomes - immunology Physiological aspects RNA, Small Interfering Sinuses Spleen - immunology Spleen - parasitology Streptococcus infections Viral infections |
| title | Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7 |
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