MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum.
Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these resp...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-04-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC2658807?pdf=render |
| _version_ | 1818600549995511808 |
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| author | Win Surachetpong Naresh Singh Kong Wai Cheung Shirley Luckhart |
| author_facet | Win Surachetpong Naresh Singh Kong Wai Cheung Shirley Luckhart |
| author_sort | Win Surachetpong |
| collection | DOAJ |
| description | Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-beta1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-beta1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-beta1, inhibition of ERK phosphorylation increased TGF-beta1-induced expression of the anti-parasite effector gene nitric oxide synthase (NOS), suggesting that increasing levels of ERK activation negatively feed back on induced NOS expression. At infection levels similar to those found in nature, inhibition of ERK activation reduced P. falciparum oocyst loads and infection prevalence in A. stephensi and enhanced TGF-beta1-mediated control of P. falciparum development. Taken together, our data demonstrate that malaria parasite development in the mosquito is regulated by a conserved MAPK signaling pathway that mediates the effects of an ingested cytokine. |
| first_indexed | 2024-12-16T12:37:16Z |
| format | Article |
| id | doaj.art-92e5e1f62e104b90af1c41055d6ee516 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T12:37:16Z |
| publishDate | 2009-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-92e5e1f62e104b90af1c41055d6ee5162022-12-21T22:31:31ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-04-0154e100036610.1371/journal.ppat.1000366MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum.Win SurachetpongNaresh SinghKong Wai CheungShirley LuckhartMalaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-beta1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-beta1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-beta1, inhibition of ERK phosphorylation increased TGF-beta1-induced expression of the anti-parasite effector gene nitric oxide synthase (NOS), suggesting that increasing levels of ERK activation negatively feed back on induced NOS expression. At infection levels similar to those found in nature, inhibition of ERK activation reduced P. falciparum oocyst loads and infection prevalence in A. stephensi and enhanced TGF-beta1-mediated control of P. falciparum development. Taken together, our data demonstrate that malaria parasite development in the mosquito is regulated by a conserved MAPK signaling pathway that mediates the effects of an ingested cytokine.http://europepmc.org/articles/PMC2658807?pdf=render |
| spellingShingle | Win Surachetpong Naresh Singh Kong Wai Cheung Shirley Luckhart MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. PLoS Pathogens |
| title | MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. |
| title_full | MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. |
| title_fullStr | MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. |
| title_full_unstemmed | MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. |
| title_short | MAPK ERK signaling regulates the TGF-beta1-dependent mosquito response to Plasmodium falciparum. |
| title_sort | mapk erk signaling regulates the tgf beta1 dependent mosquito response to plasmodium falciparum |
| url | http://europepmc.org/articles/PMC2658807?pdf=render |
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