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Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2) with Leishmania burden in canine visceral leishmaniasis
Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic...
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Published in: | PloS one 2013-10, Vol.8 (10), p.e73873-e73873 |
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creator | do Nascimento, Paulo Ricardo Porfírio Martins, Daniella Regina Arantes Monteiro, Glória Regina Góis Queiroz, Paula Vivianne Freire-Neto, Francisco Paulo Queiroz, José Wilton Morais Lima, Adila Lorena Jeronimo, Selma Maria Bezerra |
description | Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection. |
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We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0073873</identifier><identifier>PMID: 24146743</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Albumin ; Animals ; Cytokines ; Dog Diseases - genetics ; Dog Diseases - immunology ; Dog Diseases - parasitology ; Dogs ; Enzyme-linked immunosorbent assay ; Female ; Gene Expression ; Host-Parasite Interactions ; Immune response ; Immune system ; Infection ; Infections ; Inflammation ; Interferon-gamma - genetics ; Interferon-gamma - immunology ; Interleukin 10 ; Interleukin-10 - genetics ; Interleukin-10 - immunology ; Iron ; Iron - immunology ; Iron - metabolism ; Iron regulatory protein ; Iron Regulatory Protein 2 - genetics ; Iron Regulatory Protein 2 - immunology ; Leishmania ; Leishmania infantum ; Leishmania infantum - immunology ; Leishmania infantum - pathogenicity ; Leishmaniasis, Visceral - genetics ; Leishmaniasis, Visceral - immunology ; Leishmaniasis, Visceral - parasitology ; Leishmaniasis, Visceral - veterinary ; Male ; Medical research ; Parasite Load ; Parasitic diseases ; Proteins ; Quartiles ; Serum Albumin - immunology ; Serum Albumin - metabolism ; Severity of Illness Index ; Spleen ; Spleen - immunology ; Spleen - parasitology ; Spleen - pathology ; Tropical diseases ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - immunology ; Tumor necrosis factor-α ; Vector-borne diseases ; Visceral leishmaniasis ; γ-Interferon</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e73873-e73873</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Nascimento et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Nascimento et al 2013 Nascimento et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-4a5c09768f9b387fbd86c1d942bdb904a7aedbff94f6442d5309ff57269cc8263</citedby><cites>FETCH-LOGICAL-c593t-4a5c09768f9b387fbd86c1d942bdb904a7aedbff94f6442d5309ff57269cc8263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1441432799/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1441432799?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24146743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Brayton, Kelly A.</contributor><creatorcontrib>do Nascimento, Paulo Ricardo Porfírio</creatorcontrib><creatorcontrib>Martins, Daniella Regina Arantes</creatorcontrib><creatorcontrib>Monteiro, Glória Regina Góis</creatorcontrib><creatorcontrib>Queiroz, Paula Vivianne</creatorcontrib><creatorcontrib>Freire-Neto, Francisco Paulo</creatorcontrib><creatorcontrib>Queiroz, José Wilton</creatorcontrib><creatorcontrib>Morais Lima, Adila Lorena</creatorcontrib><creatorcontrib>Jeronimo, Selma Maria Bezerra</creatorcontrib><title>Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2) with Leishmania burden in canine visceral leishmaniasis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.</description><subject>Albumin</subject><subject>Animals</subject><subject>Cytokines</subject><subject>Dog Diseases - genetics</subject><subject>Dog Diseases - immunology</subject><subject>Dog Diseases - parasitology</subject><subject>Dogs</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Host-Parasite Interactions</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Infection</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - immunology</subject><subject>Interleukin 10</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-10 - immunology</subject><subject>Iron</subject><subject>Iron - immunology</subject><subject>Iron - metabolism</subject><subject>Iron regulatory protein</subject><subject>Iron Regulatory Protein 2 - genetics</subject><subject>Iron Regulatory Protein 2 - immunology</subject><subject>Leishmania</subject><subject>Leishmania infantum</subject><subject>Leishmania infantum - immunology</subject><subject>Leishmania infantum - pathogenicity</subject><subject>Leishmaniasis, Visceral - genetics</subject><subject>Leishmaniasis, Visceral - immunology</subject><subject>Leishmaniasis, Visceral - parasitology</subject><subject>Leishmaniasis, Visceral - veterinary</subject><subject>Male</subject><subject>Medical research</subject><subject>Parasite Load</subject><subject>Parasitic diseases</subject><subject>Proteins</subject><subject>Quartiles</subject><subject>Serum Albumin - immunology</subject><subject>Serum Albumin - metabolism</subject><subject>Severity of Illness Index</subject><subject>Spleen</subject><subject>Spleen - immunology</subject><subject>Spleen - parasitology</subject><subject>Spleen - pathology</subject><subject>Tropical diseases</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Tumor necrosis factor-α</subject><subject>Vector-borne diseases</subject><subject>Visceral leishmaniasis</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkstuEzEYhUcIREvhDRBYYlMWCb7NeLypFFVcIkUCIVhbviYOM3awZ4ryAjw3TjONWlTNwmP7-499fp-qeo3gHBGGPmzjmILs5rsY7BxCRlpGnlTniBM8azAkT-_9n1Uvct5CWJO2aZ5XZ5gi2jBKzqu_i5yj9nLwMYDowC7FmQ-uk30vh5j2QO-H-MsHm4EMBvhUsGTXY3fcLfhgfQAYXC6_f8PvwR8_bMDK-rzpZfASqDEZG0BBdJkHC2581jbJDnQnKPv8snrmZJftq2m8qH5--vjj-sts9fXz8nqxmumak2FGZa0hZ03ruCp-nTJto5HhFCujOKSSSWuUc5y6hlJsagK5czXDDde6xQ25qN4edXddzGJqYRaIloYQzDgvxPJImCi3Ypd8L9NeROnF7UJMayHT4HVnBSJUK4qsNVRTaCBXrWprzGpJMVEcFa2r6bRR9dZoG4bi_IHow53gN2IdbwRhvGaIFYHLSSDF36PNg-gP7es6GWwcb-9NCaeEkoK--w993N1ErWUxUB46lnP1QVQsKGsJRgTBQs0focpnbO91yZvzZf1BAT0W6BRzTtadPCIoDmm9u4w4pFVMaS1lb-7351R0F0_yD2x66Mg</recordid><startdate>20131011</startdate><enddate>20131011</enddate><creator>do Nascimento, Paulo Ricardo Porfírio</creator><creator>Martins, Daniella Regina Arantes</creator><creator>Monteiro, Glória Regina Góis</creator><creator>Queiroz, Paula Vivianne</creator><creator>Freire-Neto, Francisco Paulo</creator><creator>Queiroz, José Wilton</creator><creator>Morais Lima, Adila Lorena</creator><creator>Jeronimo, Selma Maria Bezerra</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131011</creationdate><title>Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2) with Leishmania burden in canine visceral leishmaniasis</title><author>do Nascimento, Paulo Ricardo Porfírio ; Martins, Daniella Regina Arantes ; Monteiro, Glória Regina Góis ; Queiroz, Paula Vivianne ; Freire-Neto, Francisco Paulo ; Queiroz, José Wilton ; Morais Lima, Adila Lorena ; Jeronimo, Selma Maria Bezerra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-4a5c09768f9b387fbd86c1d942bdb904a7aedbff94f6442d5309ff57269cc8263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Albumin</topic><topic>Animals</topic><topic>Cytokines</topic><topic>Dog Diseases - genetics</topic><topic>Dog Diseases - immunology</topic><topic>Dog Diseases - parasitology</topic><topic>Dogs</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Host-Parasite Interactions</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Infection</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Interferon-gamma - genetics</topic><topic>Interferon-gamma - immunology</topic><topic>Interleukin 10</topic><topic>Interleukin-10 - genetics</topic><topic>Interleukin-10 - immunology</topic><topic>Iron</topic><topic>Iron - immunology</topic><topic>Iron - metabolism</topic><topic>Iron regulatory protein</topic><topic>Iron Regulatory Protein 2 - genetics</topic><topic>Iron Regulatory Protein 2 - immunology</topic><topic>Leishmania</topic><topic>Leishmania infantum</topic><topic>Leishmania infantum - immunology</topic><topic>Leishmania infantum - pathogenicity</topic><topic>Leishmaniasis, Visceral - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>do Nascimento, Paulo Ricardo Porfírio</au><au>Martins, Daniella Regina Arantes</au><au>Monteiro, Glória Regina Góis</au><au>Queiroz, Paula Vivianne</au><au>Freire-Neto, Francisco Paulo</au><au>Queiroz, José Wilton</au><au>Morais Lima, Adila Lorena</au><au>Jeronimo, Selma Maria Bezerra</au><au>Brayton, Kelly A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2) with Leishmania burden in canine visceral leishmaniasis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-10-11</date><risdate>2013</risdate><volume>8</volume><issue>10</issue><spage>e73873</spage><epage>e73873</epage><pages>e73873-e73873</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24146743</pmid><doi>10.1371/journal.pone.0073873</doi><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_1441432799 |
source | Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central |
subjects | Albumin Animals Cytokines Dog Diseases - genetics Dog Diseases - immunology Dog Diseases - parasitology Dogs Enzyme-linked immunosorbent assay Female Gene Expression Host-Parasite Interactions Immune response Immune system Infection Infections Inflammation Interferon-gamma - genetics Interferon-gamma - immunology Interleukin 10 Interleukin-10 - genetics Interleukin-10 - immunology Iron Iron - immunology Iron - metabolism Iron regulatory protein Iron Regulatory Protein 2 - genetics Iron Regulatory Protein 2 - immunology Leishmania Leishmania infantum Leishmania infantum - immunology Leishmania infantum - pathogenicity Leishmaniasis, Visceral - genetics Leishmaniasis, Visceral - immunology Leishmaniasis, Visceral - parasitology Leishmaniasis, Visceral - veterinary Male Medical research Parasite Load Parasitic diseases Proteins Quartiles Serum Albumin - immunology Serum Albumin - metabolism Severity of Illness Index Spleen Spleen - immunology Spleen - parasitology Spleen - pathology Tropical diseases Tumor necrosis factor Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology Tumor necrosis factor-α Vector-borne diseases Visceral leishmaniasis γ-Interferon |
title | Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2) with Leishmania burden in canine visceral leishmaniasis |
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