Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages.
BACKGROUND: Sand fly saliva contains molecules that modify the host's hemostasis and immune responses. Nevertheless, the role played by this saliva in the induction of key elements of inflammatory responses, such as lipid bodies (LB, also known as lipid droplets) and eicosanoids, has been poorl...
Published in: | PLoS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:4fee4fa578384221bd92374df00f7f5e 2023-05-15T15:16:32+02:00 Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages. Théo Araújo-Santos Deboraci Brito Prates Bruno Bezerril Andrade Danielle Oliveira Nascimento Jorge Clarêncio Petter F Entringer Alan B Carneiro Mário A C Silva-Neto José Carlos Miranda Cláudia Ida Brodskyn Aldina Barral Patrícia T Bozza Valéria Matos Borges 2010-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000873 https://doaj.org/article/4fee4fa578384221bd92374df00f7f5e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2970534?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0000873 https://doaj.org/article/4fee4fa578384221bd92374df00f7f5e PLoS Neglected Tropical Diseases, Vol 4, Iss 11, p e873 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000873 2022-12-31T02:17:06Z BACKGROUND: Sand fly saliva contains molecules that modify the host's hemostasis and immune responses. Nevertheless, the role played by this saliva in the induction of key elements of inflammatory responses, such as lipid bodies (LB, also known as lipid droplets) and eicosanoids, has been poorly investigated. LBs are cytoplasmic organelles involved in arachidonic acid metabolism that form eicosanoids in response to inflammatory stimuli. In this study, we assessed the role of salivary gland sonicate (SGS) from Lutzomyia (L.) longipalpis, a Leishmania infantum chagasi vector, in the induction of LBs and eicosanoid production by macrophages in vitro and ex vivo. METHODOLOGY/PRINCIPAL FINDINGS: Different doses of L. longipalpis SGS were injected into peritoneal cavities of C57BL/6 mice. SGS induced increased macrophage and neutrophil recruitment into the peritoneal cavity at different time points. Sand fly saliva enhanced PGE₂ and LTB₄ production by harvested peritoneal leukocytes after ex vivo stimulation with a calcium ionophore. At three and six hours post-injection, L. longipalpis SGS induced more intense LB staining in macrophages, but not in neutrophils, compared with mice injected with saline. Moreover, macrophages harvested by peritoneal lavage and stimulated with SGS in vitro presented a dose- and time-dependent increase in LB numbers, which was correlated with increased PGE₂ production. Furthermore, COX-2 and PGE-synthase co-localized within the LBs induced by L. longipalpis saliva. PGE₂ production by macrophages induced by SGS was abrogated by treatment with NS-398, a COX-2 inhibitor. Strikingly, SGS triggered ERK-1/2 and PKC-α phosphorylation, and blockage of the ERK-1/2 and PKC-α pathways inhibited the SGS effect on PGE₂ production by macrophages. CONCLUSION: In sum, our results show that L. longipalpis saliva induces lipid body formation and PGE₂ production by macrophages ex vivo and in vitro via the ERK-1/2 and PKC-α signaling pathways. This study provides new insights regarding the pharmacological ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 4 11 e873 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Théo Araújo-Santos Deboraci Brito Prates Bruno Bezerril Andrade Danielle Oliveira Nascimento Jorge Clarêncio Petter F Entringer Alan B Carneiro Mário A C Silva-Neto José Carlos Miranda Cláudia Ida Brodskyn Aldina Barral Patrícia T Bozza Valéria Matos Borges Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Sand fly saliva contains molecules that modify the host's hemostasis and immune responses. Nevertheless, the role played by this saliva in the induction of key elements of inflammatory responses, such as lipid bodies (LB, also known as lipid droplets) and eicosanoids, has been poorly investigated. LBs are cytoplasmic organelles involved in arachidonic acid metabolism that form eicosanoids in response to inflammatory stimuli. In this study, we assessed the role of salivary gland sonicate (SGS) from Lutzomyia (L.) longipalpis, a Leishmania infantum chagasi vector, in the induction of LBs and eicosanoid production by macrophages in vitro and ex vivo. METHODOLOGY/PRINCIPAL FINDINGS: Different doses of L. longipalpis SGS were injected into peritoneal cavities of C57BL/6 mice. SGS induced increased macrophage and neutrophil recruitment into the peritoneal cavity at different time points. Sand fly saliva enhanced PGE₂ and LTB₄ production by harvested peritoneal leukocytes after ex vivo stimulation with a calcium ionophore. At three and six hours post-injection, L. longipalpis SGS induced more intense LB staining in macrophages, but not in neutrophils, compared with mice injected with saline. Moreover, macrophages harvested by peritoneal lavage and stimulated with SGS in vitro presented a dose- and time-dependent increase in LB numbers, which was correlated with increased PGE₂ production. Furthermore, COX-2 and PGE-synthase co-localized within the LBs induced by L. longipalpis saliva. PGE₂ production by macrophages induced by SGS was abrogated by treatment with NS-398, a COX-2 inhibitor. Strikingly, SGS triggered ERK-1/2 and PKC-α phosphorylation, and blockage of the ERK-1/2 and PKC-α pathways inhibited the SGS effect on PGE₂ production by macrophages. CONCLUSION: In sum, our results show that L. longipalpis saliva induces lipid body formation and PGE₂ production by macrophages ex vivo and in vitro via the ERK-1/2 and PKC-α signaling pathways. This study provides new insights regarding the pharmacological ... |
format |
Article in Journal/Newspaper |
author |
Théo Araújo-Santos Deboraci Brito Prates Bruno Bezerril Andrade Danielle Oliveira Nascimento Jorge Clarêncio Petter F Entringer Alan B Carneiro Mário A C Silva-Neto José Carlos Miranda Cláudia Ida Brodskyn Aldina Barral Patrícia T Bozza Valéria Matos Borges |
author_facet |
Théo Araújo-Santos Deboraci Brito Prates Bruno Bezerril Andrade Danielle Oliveira Nascimento Jorge Clarêncio Petter F Entringer Alan B Carneiro Mário A C Silva-Neto José Carlos Miranda Cláudia Ida Brodskyn Aldina Barral Patrícia T Bozza Valéria Matos Borges |
author_sort |
Théo Araújo-Santos |
title |
Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages. |
title_short |
Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages. |
title_full |
Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages. |
title_fullStr |
Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages. |
title_full_unstemmed |
Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E₂ production in murine macrophages. |
title_sort |
lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin e₂ production in murine macrophages. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000873 https://doaj.org/article/4fee4fa578384221bd92374df00f7f5e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 11, p e873 (2010) |
op_relation |
http://europepmc.org/articles/PMC2970534?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0000873 https://doaj.org/article/4fee4fa578384221bd92374df00f7f5e |
op_doi |
https://doi.org/10.1371/journal.pntd.0000873 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
4 |
container_issue |
11 |
container_start_page |
e873 |
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1766346824711405568 |