Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis
During infections involving intracellular pathogens, iron performs a double-edged function by providing the pathogen with nutrients, but also boosts the host's antimicrobial arsenal. Although the role of iron has been described in visceral leishmaniasis, information regarding its status in the...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2020-02, Vol.14 (2), p.e0007991-e0007991 |
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| creator | Dighal, Aishwarya Mukhopadhyay, Debanjan Sengupta, Ritika Moulik, Srija Mukherjee, Shibabrata Roy, Susmita Chaudhuri, Surya Jyati Das, Nilay K Chatterjee, Mitali |
| description | During infections involving intracellular pathogens, iron performs a double-edged function by providing the pathogen with nutrients, but also boosts the host's antimicrobial arsenal. Although the role of iron has been described in visceral leishmaniasis, information regarding its status in the dermal sequel, Post Kala-azar Dermal Leishmaniasis (PKDL) remains limited. Accordingly, this study aimed to establish the status of iron within monocytes/macrophages of PKDL cases.
The intramonocytic labile iron pool (LIP), status of CD163 (hemoglobin-haptoglobin scavenging receptor) and CD71 (transferrin receptor, Tfr) were evaluated within CD14+ monocytes by flow cytometry, and soluble CD163 by ELISA. At the lesional sites, Fe3+ status was evaluated by Prussian blue staining, parasite load by qPCR, while the mRNA expression of Tfr (TfR1/CD71), CD163, divalent metal transporter-1 (DMT-1), Lipocalin-2 (Lcn-2), Heme-oxygenase-1 (HO-1), Ferritin, Natural resistance-associated macrophage protein (NRAMP-1) and Ferroportin (Fpn-1) was evaluated by droplet digital PCR. Circulating monocytes demonstrated elevated levels of CD71, CD163 and soluble CD163, which corroborated with an enhanced lesional mRNA expression of TfR, CD163, DMT1 and Lcn-2. Additionally, the LIP was raised along with an elevated mRNA expression of ferritin and HO-1, as also iron exporters NRAMP-1 and Fpn-1.
In monocytes/macrophages of PKDL cases, enhancement of the iron influx gateways (TfR, CD163, DMT-1 and Lcn-2) possibly accounted for the enhanced LIP. However, enhancement of the iron exporters (NRAMP-1 and Fpn-1) defied the classical Ferritinlow/Ferroportinhigh phenotype of alternatively activated macrophages. The creation of such a pro-parasitic environment suggests incorporation of chemotherapeutic strategies wherein the availability of iron to the parasite can be restricted. |
| doi_str_mv | 10.1371/journal.pntd.0007991 |
| format | Article |
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The intramonocytic labile iron pool (LIP), status of CD163 (hemoglobin-haptoglobin scavenging receptor) and CD71 (transferrin receptor, Tfr) were evaluated within CD14+ monocytes by flow cytometry, and soluble CD163 by ELISA. At the lesional sites, Fe3+ status was evaluated by Prussian blue staining, parasite load by qPCR, while the mRNA expression of Tfr (TfR1/CD71), CD163, divalent metal transporter-1 (DMT-1), Lipocalin-2 (Lcn-2), Heme-oxygenase-1 (HO-1), Ferritin, Natural resistance-associated macrophage protein (NRAMP-1) and Ferroportin (Fpn-1) was evaluated by droplet digital PCR. Circulating monocytes demonstrated elevated levels of CD71, CD163 and soluble CD163, which corroborated with an enhanced lesional mRNA expression of TfR, CD163, DMT1 and Lcn-2. Additionally, the LIP was raised along with an elevated mRNA expression of ferritin and HO-1, as also iron exporters NRAMP-1 and Fpn-1.
In monocytes/macrophages of PKDL cases, enhancement of the iron influx gateways (TfR, CD163, DMT-1 and Lcn-2) possibly accounted for the enhanced LIP. However, enhancement of the iron exporters (NRAMP-1 and Fpn-1) defied the classical Ferritinlow/Ferroportinhigh phenotype of alternatively activated macrophages. The creation of such a pro-parasitic environment suggests incorporation of chemotherapeutic strategies wherein the availability of iron to the parasite can be restricted.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0007991</identifier><identifier>PMID: 32023254</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Antigens, CD - genetics ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - genetics ; Antigens, Differentiation, Myelomonocytic - metabolism ; Authorship ; Biology and Life Sciences ; Biopsy ; Care and treatment ; Cation Transport Proteins - genetics ; Cation Transport Proteins - metabolism ; CD14 antigen ; CD163 antigen ; Chemotherapy ; Circumcision ; Deoxyribonucleic acid ; Dermatology ; Divalent metal transporter-1 ; DNA ; ELISA ; Enzyme-linked immunosorbent assay ; Female ; Ferritin ; Flow cytometry ; Gene expression ; Glycosylated hemoglobin ; Haptoglobin ; Health aspects ; Heme ; Hemoglobin ; Hemoglobins ; Humans ; India ; Infection ; Iron ; Iron - metabolism ; Iron compounds ; Leishmania donovani - drug effects ; Leishmania donovani - physiology ; Leishmaniasis ; Leishmaniasis, Cutaneous - metabolism ; Leishmaniasis, Cutaneous - parasitology ; Lipocalin ; Lipocalin-2 - genetics ; Lipocalin-2 - metabolism ; Macrophages ; Macrophages - metabolism ; Male ; Medical education ; Medical research ; Medicine and Health Sciences ; Messenger RNA ; Metals ; Monocytes ; Monocytes - metabolism ; Nramp protein ; Nucleotide sequence ; Nutrients ; Oxygenase ; Parasites ; Parasitic diseases ; Pathogenic microorganisms ; Pathogens ; PCR ; Pharmacology ; Phenotypes ; Physical Sciences ; Pigments ; Plasma ; Receptors ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Receptors, Transferrin - genetics ; Receptors, Transferrin - metabolism ; RNA ; Scavenging ; Skin ; Software ; Transferrin ; Transferrins ; Tropical diseases ; Vector-borne diseases ; Visceral leishmaniasis ; Young Adult</subject><ispartof>PLoS neglected tropical diseases, 2020-02, Vol.14 (2), p.e0007991-e0007991</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Dighal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2020 Dighal et al 2020 Dighal et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-ec87f98fafe273a352f93a57ea12935bec9e646e3c3f29a991ad98f56f4305863</citedby><cites>FETCH-LOGICAL-c624t-ec87f98fafe273a352f93a57ea12935bec9e646e3c3f29a991ad98f56f4305863</cites><orcidid>0000-0002-5123-6019 ; 0000-0003-1654-091X ; 0000-0002-8921-4106</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001907/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001907/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32023254$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Roy, Syamal</contributor><creatorcontrib>Dighal, Aishwarya</creatorcontrib><creatorcontrib>Mukhopadhyay, Debanjan</creatorcontrib><creatorcontrib>Sengupta, Ritika</creatorcontrib><creatorcontrib>Moulik, Srija</creatorcontrib><creatorcontrib>Mukherjee, Shibabrata</creatorcontrib><creatorcontrib>Roy, Susmita</creatorcontrib><creatorcontrib>Chaudhuri, Surya Jyati</creatorcontrib><creatorcontrib>Das, Nilay K</creatorcontrib><creatorcontrib>Chatterjee, Mitali</creatorcontrib><title>Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>During infections involving intracellular pathogens, iron performs a double-edged function by providing the pathogen with nutrients, but also boosts the host's antimicrobial arsenal. Although the role of iron has been described in visceral leishmaniasis, information regarding its status in the dermal sequel, Post Kala-azar Dermal Leishmaniasis (PKDL) remains limited. Accordingly, this study aimed to establish the status of iron within monocytes/macrophages of PKDL cases.
The intramonocytic labile iron pool (LIP), status of CD163 (hemoglobin-haptoglobin scavenging receptor) and CD71 (transferrin receptor, Tfr) were evaluated within CD14+ monocytes by flow cytometry, and soluble CD163 by ELISA. At the lesional sites, Fe3+ status was evaluated by Prussian blue staining, parasite load by qPCR, while the mRNA expression of Tfr (TfR1/CD71), CD163, divalent metal transporter-1 (DMT-1), Lipocalin-2 (Lcn-2), Heme-oxygenase-1 (HO-1), Ferritin, Natural resistance-associated macrophage protein (NRAMP-1) and Ferroportin (Fpn-1) was evaluated by droplet digital PCR. Circulating monocytes demonstrated elevated levels of CD71, CD163 and soluble CD163, which corroborated with an enhanced lesional mRNA expression of TfR, CD163, DMT1 and Lcn-2. Additionally, the LIP was raised along with an elevated mRNA expression of ferritin and HO-1, as also iron exporters NRAMP-1 and Fpn-1.
In monocytes/macrophages of PKDL cases, enhancement of the iron influx gateways (TfR, CD163, DMT-1 and Lcn-2) possibly accounted for the enhanced LIP. However, enhancement of the iron exporters (NRAMP-1 and Fpn-1) defied the classical Ferritinlow/Ferroportinhigh phenotype of alternatively activated macrophages. The creation of such a pro-parasitic environment suggests incorporation of chemotherapeutic strategies wherein the availability of iron to the parasite can be restricted.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - genetics</subject><subject>Antigens, Differentiation, Myelomonocytic - metabolism</subject><subject>Authorship</subject><subject>Biology and Life Sciences</subject><subject>Biopsy</subject><subject>Care and treatment</subject><subject>Cation Transport Proteins - genetics</subject><subject>Cation Transport Proteins - metabolism</subject><subject>CD14 antigen</subject><subject>CD163 antigen</subject><subject>Chemotherapy</subject><subject>Circumcision</subject><subject>Deoxyribonucleic acid</subject><subject>Dermatology</subject><subject>Divalent metal transporter-1</subject><subject>DNA</subject><subject>ELISA</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Ferritin</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Glycosylated hemoglobin</subject><subject>Haptoglobin</subject><subject>Health aspects</subject><subject>Heme</subject><subject>Hemoglobin</subject><subject>Hemoglobins</subject><subject>Humans</subject><subject>India</subject><subject>Infection</subject><subject>Iron</subject><subject>Iron - metabolism</subject><subject>Iron compounds</subject><subject>Leishmania donovani - drug effects</subject><subject>Leishmania donovani - physiology</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis, Cutaneous - metabolism</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Lipocalin</subject><subject>Lipocalin-2 - genetics</subject><subject>Lipocalin-2 - metabolism</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Medical education</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Messenger RNA</subject><subject>Metals</subject><subject>Monocytes</subject><subject>Monocytes - metabolism</subject><subject>Nramp protein</subject><subject>Nucleotide sequence</subject><subject>Nutrients</subject><subject>Oxygenase</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Pathogenic microorganisms</subject><subject>Pathogens</subject><subject>PCR</subject><subject>Pharmacology</subject><subject>Phenotypes</subject><subject>Physical Sciences</subject><subject>Pigments</subject><subject>Plasma</subject><subject>Receptors</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Transferrin - genetics</subject><subject>Receptors, Transferrin - metabolism</subject><subject>RNA</subject><subject>Scavenging</subject><subject>Skin</subject><subject>Software</subject><subject>Transferrin</subject><subject>Transferrins</subject><subject>Tropical diseases</subject><subject>Vector-borne diseases</subject><subject>Visceral leishmaniasis</subject><subject>Young Adult</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkl2LEzEUhgdR3HX1H4gOCOJNayaZTCY3C8viR2FBL_Q6nGZO2nQzSU1SRX-9qZ1dWlkCSUie9z0fnKp62ZB5w0TzfhN20YObb30e5oQQIWXzqDpvJOMzKhh_fHQ_q56ltCGES943T6szRglllLfn1c0iBl_nCMZYfWv9qra-3kK26HOqf9m8rhd-sODrryHl-hYczOAPxHrAOIKrHdq0HsFbSDY9r54YcAlfTOdF9f3jh2_Xn2c3Xz4trq9uZrqjbZ6h7oWRvQGDJTlgnBrJgAuEhpaMl6gldm2HTDNDJZS6YCg470zLCO87dlG9PvhuXUhqakRSlAkhSmGyL8TiQAwBNmob7Qjxtwpg1b-HEFcKYrbaoeIlEqdcDks-tL3WS0oABEcAiXJgWLwup2i75YiDLp2J4E5MT3-8XatV-KkEIY0kohi8mwxi-LHDlNVok0bnwGPY7fPmlHDakbagb_5DH65uolZQCrDehBJX703VVdd0nLZlL9T8AaqsAUerg0djy_uJ4O2RYI3g8joFt8s2-HQKtgdQx5BSRHPfjIao_XDeZa32w6mm4SyyV8eNvBfdTSP7C2Va4LI</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Dighal, Aishwarya</creator><creator>Mukhopadhyay, Debanjan</creator><creator>Sengupta, Ritika</creator><creator>Moulik, Srija</creator><creator>Mukherjee, Shibabrata</creator><creator>Roy, Susmita</creator><creator>Chaudhuri, Surya Jyati</creator><creator>Das, Nilay K</creator><creator>Chatterjee, Mitali</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>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5123-6019</orcidid><orcidid>https://orcid.org/0000-0003-1654-091X</orcidid><orcidid>https://orcid.org/0000-0002-8921-4106</orcidid></search><sort><creationdate>20200201</creationdate><title>Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis</title><author>Dighal, Aishwarya ; Mukhopadhyay, Debanjan ; Sengupta, Ritika ; Moulik, Srija ; Mukherjee, Shibabrata ; Roy, Susmita ; Chaudhuri, Surya Jyati ; Das, Nilay K ; Chatterjee, Mitali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-ec87f98fafe273a352f93a57ea12935bec9e646e3c3f29a991ad98f56f4305863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antigens, CD - 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metabolism</topic><topic>Iron compounds</topic><topic>Leishmania donovani - drug effects</topic><topic>Leishmania donovani - physiology</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis, Cutaneous - metabolism</topic><topic>Leishmaniasis, Cutaneous - parasitology</topic><topic>Lipocalin</topic><topic>Lipocalin-2 - genetics</topic><topic>Lipocalin-2 - metabolism</topic><topic>Macrophages</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Medical education</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Messenger RNA</topic><topic>Metals</topic><topic>Monocytes</topic><topic>Monocytes - metabolism</topic><topic>Nramp protein</topic><topic>Nucleotide sequence</topic><topic>Nutrients</topic><topic>Oxygenase</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Pathogenic microorganisms</topic><topic>Pathogens</topic><topic>PCR</topic><topic>Pharmacology</topic><topic>Phenotypes</topic><topic>Physical Sciences</topic><topic>Pigments</topic><topic>Plasma</topic><topic>Receptors</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, Transferrin - genetics</topic><topic>Receptors, Transferrin - metabolism</topic><topic>RNA</topic><topic>Scavenging</topic><topic>Skin</topic><topic>Software</topic><topic>Transferrin</topic><topic>Transferrins</topic><topic>Tropical diseases</topic><topic>Vector-borne diseases</topic><topic>Visceral leishmaniasis</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dighal, Aishwarya</creatorcontrib><creatorcontrib>Mukhopadhyay, Debanjan</creatorcontrib><creatorcontrib>Sengupta, Ritika</creatorcontrib><creatorcontrib>Moulik, Srija</creatorcontrib><creatorcontrib>Mukherjee, Shibabrata</creatorcontrib><creatorcontrib>Roy, Susmita</creatorcontrib><creatorcontrib>Chaudhuri, Surya Jyati</creatorcontrib><creatorcontrib>Das, Nilay K</creatorcontrib><creatorcontrib>Chatterjee, Mitali</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dighal, Aishwarya</au><au>Mukhopadhyay, Debanjan</au><au>Sengupta, Ritika</au><au>Moulik, Srija</au><au>Mukherjee, Shibabrata</au><au>Roy, Susmita</au><au>Chaudhuri, Surya Jyati</au><au>Das, Nilay K</au><au>Chatterjee, Mitali</au><au>Roy, Syamal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>14</volume><issue>2</issue><spage>e0007991</spage><epage>e0007991</epage><pages>e0007991-e0007991</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>During infections involving intracellular pathogens, iron performs a double-edged function by providing the pathogen with nutrients, but also boosts the host's antimicrobial arsenal. Although the role of iron has been described in visceral leishmaniasis, information regarding its status in the dermal sequel, Post Kala-azar Dermal Leishmaniasis (PKDL) remains limited. Accordingly, this study aimed to establish the status of iron within monocytes/macrophages of PKDL cases.
The intramonocytic labile iron pool (LIP), status of CD163 (hemoglobin-haptoglobin scavenging receptor) and CD71 (transferrin receptor, Tfr) were evaluated within CD14+ monocytes by flow cytometry, and soluble CD163 by ELISA. At the lesional sites, Fe3+ status was evaluated by Prussian blue staining, parasite load by qPCR, while the mRNA expression of Tfr (TfR1/CD71), CD163, divalent metal transporter-1 (DMT-1), Lipocalin-2 (Lcn-2), Heme-oxygenase-1 (HO-1), Ferritin, Natural resistance-associated macrophage protein (NRAMP-1) and Ferroportin (Fpn-1) was evaluated by droplet digital PCR. Circulating monocytes demonstrated elevated levels of CD71, CD163 and soluble CD163, which corroborated with an enhanced lesional mRNA expression of TfR, CD163, DMT1 and Lcn-2. Additionally, the LIP was raised along with an elevated mRNA expression of ferritin and HO-1, as also iron exporters NRAMP-1 and Fpn-1.
In monocytes/macrophages of PKDL cases, enhancement of the iron influx gateways (TfR, CD163, DMT-1 and Lcn-2) possibly accounted for the enhanced LIP. However, enhancement of the iron exporters (NRAMP-1 and Fpn-1) defied the classical Ferritinlow/Ferroportinhigh phenotype of alternatively activated macrophages. The creation of such a pro-parasitic environment suggests incorporation of chemotherapeutic strategies wherein the availability of iron to the parasite can be restricted.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32023254</pmid><doi>10.1371/journal.pntd.0007991</doi><orcidid>https://orcid.org/0000-0002-5123-6019</orcidid><orcidid>https://orcid.org/0000-0003-1654-091X</orcidid><orcidid>https://orcid.org/0000-0002-8921-4106</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2020-02, Vol.14 (2), p.e0007991-e0007991 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_2377702398 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Adolescent Adult Antigens, CD - genetics Antigens, CD - metabolism Antigens, Differentiation, Myelomonocytic - genetics Antigens, Differentiation, Myelomonocytic - metabolism Authorship Biology and Life Sciences Biopsy Care and treatment Cation Transport Proteins - genetics Cation Transport Proteins - metabolism CD14 antigen CD163 antigen Chemotherapy Circumcision Deoxyribonucleic acid Dermatology Divalent metal transporter-1 DNA ELISA Enzyme-linked immunosorbent assay Female Ferritin Flow cytometry Gene expression Glycosylated hemoglobin Haptoglobin Health aspects Heme Hemoglobin Hemoglobins Humans India Infection Iron Iron - metabolism Iron compounds Leishmania donovani - drug effects Leishmania donovani - physiology Leishmaniasis Leishmaniasis, Cutaneous - metabolism Leishmaniasis, Cutaneous - parasitology Lipocalin Lipocalin-2 - genetics Lipocalin-2 - metabolism Macrophages Macrophages - metabolism Male Medical education Medical research Medicine and Health Sciences Messenger RNA Metals Monocytes Monocytes - metabolism Nramp protein Nucleotide sequence Nutrients Oxygenase Parasites Parasitic diseases Pathogenic microorganisms Pathogens PCR Pharmacology Phenotypes Physical Sciences Pigments Plasma Receptors Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Receptors, Transferrin - genetics Receptors, Transferrin - metabolism RNA Scavenging Skin Software Transferrin Transferrins Tropical diseases Vector-borne diseases Visceral leishmaniasis Young Adult |
| title | Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis |
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