Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturation
<p>Abstract</p> <p>Background</p> <p>Infection with <it>Plasmodium </it>is the cause of malaria, a disease characterized by a high inflammatory response in the blood. Dendritic cells (DC) participate in both adaptive and innate immune responses, influencing...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-03-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/9/1/64 |
| _version_ | 1818379396538433536 |
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| author | Ocaña-Morgner Carlos Galan-Rodriguez Cristina Carapau Daniel Bettiol Esther Rodriguez Ana |
| author_facet | Ocaña-Morgner Carlos Galan-Rodriguez Cristina Carapau Daniel Bettiol Esther Rodriguez Ana |
| author_sort | Ocaña-Morgner Carlos |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Infection with <it>Plasmodium </it>is the cause of malaria, a disease characterized by a high inflammatory response in the blood. Dendritic cells (DC) participate in both adaptive and innate immune responses, influencing the generation of inflammatory responses. DC can be activated through different receptors, which recognize specific molecules in microbes and induce the maturation of DC.</p> <p>Methods</p> <p>Using <it>Plasmodium yoelii</it>, a rodent malaria model, the effect of <it>Plasmodium</it>-infected erythrocytes on DC maturation and TLR responses have been analysed.</p> <p>Results</p> <p>It was found that intact erythrocytes infected with <it>P. yoelii </it>do not induce maturation of DC unless they are lysed, suggesting that accessibility of parasite inflammatory molecules to their receptors is a key issue in the activation of DC by <it>P. yoelii</it>. This activation is independent of MyD88. It was also observed that pre-incubation of DC with intact <it>P. yoelii</it>-infected erythrocytes inhibits the maturation response of DC to other TLR stimuli. The inhibition of maturation of DC is reversible, parasite-specific and increases with the stage of parasite development, with complete inhibition induced by schizonts (mature infected erythrocytes). <it>Plasmodium yoelii</it>-infected erythrocytes induce a broad inhibitory effect rendering DC non-responsive to ligands for TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9.</p> <p>Conclusions</p> <p>Despite the presence of inflammatory molecules within <it>Plasmodium</it>-infected erythrocytes, which are probably responsible for DC maturation induced by lysates, intact <it>Plasmodium</it>-infected erythrocytes induce a general inhibition of TLR responsiveness in DC. The observed effect on DC could play an important role in the pathology and suboptimal immune response observed during the disease. These results help to explain why immune functions are altered during malaria, and provide a system for the identification of a parasite-derived broad inhibitor of TLR-mediated signaling pathways.</p> |
| first_indexed | 2024-12-14T02:02:07Z |
| format | Article |
| id | doaj.art-e1f5819c39e249918c557f4e827d3002 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-14T02:02:07Z |
| publishDate | 2010-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-e1f5819c39e249918c557f4e827d30022022-12-21T23:20:59ZengBMCMalaria Journal1475-28752010-03-01916410.1186/1475-2875-9-64Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturationOcaña-Morgner CarlosGalan-Rodriguez CristinaCarapau DanielBettiol EstherRodriguez Ana<p>Abstract</p> <p>Background</p> <p>Infection with <it>Plasmodium </it>is the cause of malaria, a disease characterized by a high inflammatory response in the blood. Dendritic cells (DC) participate in both adaptive and innate immune responses, influencing the generation of inflammatory responses. DC can be activated through different receptors, which recognize specific molecules in microbes and induce the maturation of DC.</p> <p>Methods</p> <p>Using <it>Plasmodium yoelii</it>, a rodent malaria model, the effect of <it>Plasmodium</it>-infected erythrocytes on DC maturation and TLR responses have been analysed.</p> <p>Results</p> <p>It was found that intact erythrocytes infected with <it>P. yoelii </it>do not induce maturation of DC unless they are lysed, suggesting that accessibility of parasite inflammatory molecules to their receptors is a key issue in the activation of DC by <it>P. yoelii</it>. This activation is independent of MyD88. It was also observed that pre-incubation of DC with intact <it>P. yoelii</it>-infected erythrocytes inhibits the maturation response of DC to other TLR stimuli. The inhibition of maturation of DC is reversible, parasite-specific and increases with the stage of parasite development, with complete inhibition induced by schizonts (mature infected erythrocytes). <it>Plasmodium yoelii</it>-infected erythrocytes induce a broad inhibitory effect rendering DC non-responsive to ligands for TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9.</p> <p>Conclusions</p> <p>Despite the presence of inflammatory molecules within <it>Plasmodium</it>-infected erythrocytes, which are probably responsible for DC maturation induced by lysates, intact <it>Plasmodium</it>-infected erythrocytes induce a general inhibition of TLR responsiveness in DC. The observed effect on DC could play an important role in the pathology and suboptimal immune response observed during the disease. These results help to explain why immune functions are altered during malaria, and provide a system for the identification of a parasite-derived broad inhibitor of TLR-mediated signaling pathways.</p>http://www.malariajournal.com/content/9/1/64 |
| spellingShingle | Ocaña-Morgner Carlos Galan-Rodriguez Cristina Carapau Daniel Bettiol Esther Rodriguez Ana Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturation Malaria Journal |
| title | Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturation |
| title_full | Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturation |
| title_fullStr | Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturation |
| title_full_unstemmed | Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturation |
| title_short | Dual effect of <it>Plasmodium</it>-infected erythrocytes on dendritic cell maturation |
| title_sort | dual effect of it plasmodium it infected erythrocytes on dendritic cell maturation |
| url | http://www.malariajournal.com/content/9/1/64 |
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