Plasmodium falciparum suppresses the host immune response by inducing the synthesis of insulin-like peptides (ILPs) in the mosquito Anopheles stephensi

Jose E. Pietri, Eduardo J. Pietri, Rashaun Potts, Michael A. Riehle, Shirley Luckhart

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The insulin-like peptides (ILPs) and their respective signaling and regulatory pathways are highly conserved across phyla. In invertebrates, ILPs regulate diverse physiological processes, including metabolism, reproduction, behavior, and immunity. We previously reported that blood feeding alone induced minimal changes in ILP expression in Anopheles stephensi. However, ingestion of a blood meal containing human insulin or Plasmodium falciparum, which can mimic insulin signaling, leads to significant increases in ILP expression in the head and midgut, suggesting a potential role for AsILPs in the regulation of P.falciparum sporogonic development. Here, we show that soluble P.falciparum products, but not LPS or zymosan, directly induced AsILP expression in immortalized A.stephensi cells invitro. Further, AsILP expression is dependent on signaling by the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) and phosphatidylinositol 3'-kinase (PI3K)/Akt branches of the insulin/insulin-like growth factor signaling (IIS) pathway. Inhibition of P.falciparum-induced ILPs invivo decreased parasite development through kinetically distinct effects on mosquito innate immune responses. Specifically, knockdown of AsILP4 induced early expression of immune effector genes (1-6h after infection), a pattern associated with significantly reduced parasite abundance prior to invasion of the midgut epithelium. In contrast, knockdown of AsILP3 increased later expression of the same genes (24h after infection), a pattern that was associated with significantly reduced oocyst development. These data suggest that P.falciparum parasites alter the expression of mosquito AsILPs to dampen the immune response and facilitate their development in the mosquito vector.

Original languageEnglish (US)
Pages (from-to)134-144
Number of pages11
JournalDevelopmental and Comparative Immunology
Volume53
Issue number1
DOIs
StatePublished - Nov 1 2015

Keywords

  • Anopheles
  • Immunity
  • Insulin
  • Insulin-like peptide
  • Malaria
  • Mosquito
  • NF-κB
  • Plasmodium

ASJC Scopus subject areas

  • Developmental Biology
  • Immunology

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