Induction of nitric oxide synthase and activation of signaling proteins in Anopheles mosquitoes by the malaria pigment, hemozoin

Leyla Akman-Anderson, Martin Olivier, Shirley Luckhart

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Anopheles stephensi, a major vector for malaria parasite transmission, responds to Plasmodium infection by synthesis of inflammatory levels of nitric oxide (NO), which can limit parasite development in the midgut. We have previously shown that Plasmodium falciparum glycosylphosphatidylinositols (PfGPIs) can induce A. stephensi NO synthase (AsNOS) expression in the midgut epithelium in vivo in a manner similar to the manner in which cytokines and NO are induced by PfGPIs in mammalian cells. In mosquito cells, signaling by PfGPIs and P. falciparum merozoites is mediated through Akt/protein kinase B (Akt/PKB), the mitogen-activated protein kinase kinase DSOR1, and extracellular signal-regulated kinase (ERK). In mammalian cells, a second parasite factor, malaria pigment or hemozoin (Hz), signals NOS induction through ERK- and nuclear factor kappa B-dependent pathways and has been demonstrated to be a novel proinflammatory ligand for Toll-like receptor 9. In this study, we demonstrate that Hz can also induce AsNOS gene expression in immortalized A. stephensi and Anopheles gambiae cell lines in vitro and in A. stephensi midgut tissue in vivo. In mosquito cells, Hz signaling is mediated through transforming growth factor B-associated kinase 1, Akt/PKB, ERK, and atypical protein kinase C zeta/lambda. Our results show that Hz is a prominent parasite-derived signal for Anopheles and that signaling pathways activated by PfGPIs and Hz have both unique and shared components. Together with our previous findings, our data indicate that parasite signaling of innate immunity is conserved in mosquito and mammalian cells.

Original languageEnglish (US)
Pages (from-to)4012-4019
Number of pages8
JournalInfection and Immunity
Volume75
Issue number8
DOIs
StatePublished - Aug 2007

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Anopheles
Culicidae
Nitric Oxide Synthase
Plasmodium falciparum
Glycosylphosphatidylinositols
Parasites
Extracellular Signal-Regulated MAP Kinases
Proto-Oncogene Proteins c-akt
Proteins
Malaria
Nitric Oxide
Toll-Like Receptor 9
MAP Kinase Kinase Kinases
Anopheles gambiae
Merozoites
NF-kappa B
Transforming Growth Factors
Innate Immunity
hemozoin
Phosphotransferases

ASJC Scopus subject areas

  • Immunology

Cite this

Induction of nitric oxide synthase and activation of signaling proteins in Anopheles mosquitoes by the malaria pigment, hemozoin. / Akman-Anderson, Leyla; Olivier, Martin; Luckhart, Shirley.

In: Infection and Immunity, Vol. 75, No. 8, 08.2007, p. 4012-4019.

Research output: Contribution to journalArticle

Akman-Anderson, Leyla ; Olivier, Martin ; Luckhart, Shirley. / Induction of nitric oxide synthase and activation of signaling proteins in Anopheles mosquitoes by the malaria pigment, hemozoin. In: Infection and Immunity. 2007 ; Vol. 75, No. 8. pp. 4012-4019.
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