Chemical depletion of phagocytic immune cells in Anopheles gambiae reveals dual roles of mosquito hemocytes in anti- Plasmodium immunity

Proc Natl Acad Sci U S A. 2019 Jul 9;116(28):14119-14128. doi: 10.1073/pnas.1900147116. Epub 2019 Jun 24.

Abstract

Mosquito immunity is composed of both cellular and humoral factors that provide protection from invading pathogens. Immune cells known as hemocytes, have been intricately associated with phagocytosis and innate immune signaling. However, the lack of genetic tools has limited hemocyte study despite their importance in mosquito anti-Plasmodium immunity. To address these limitations, we employ the use of a chemical-based treatment to deplete phagocytic immune cells in Anopheles gambiae, demonstrating the role of phagocytes in complement recognition and prophenoloxidase production that limit the ookinete and oocyst stages of malaria parasite development, respectively. Through these experiments, we also define specific subtypes of phagocytic immune cells in An. gambiae, providing insights beyond the morphological characteristics that traditionally define mosquito hemocyte populations. Together, this study represents a significant advancement in our understanding of the roles of mosquito phagocytes in mosquito vector competence and demonstrates the utility of clodronate liposomes as an important tool in the study of invertebrate immunity.

Keywords: Anopheles gambiae; hemocytes; innate immunity; malaria; phagocyte depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / genetics
  • Anopheles / immunology*
  • Anopheles / parasitology
  • Catechol Oxidase / genetics
  • Clodronic Acid / pharmacology
  • Complement System Proteins / immunology
  • Enzyme Precursors / genetics
  • Hemocytes / drug effects
  • Hemocytes / immunology
  • Hemocytes / parasitology
  • Humans
  • Immunity, Innate*
  • Liposomes / pharmacology
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Mosquito Vectors / immunology
  • Mosquito Vectors / parasitology
  • Oocysts / immunology
  • Phagocytes / drug effects
  • Phagocytes / immunology
  • Phagocytes / parasitology
  • Phagocytosis / drug effects
  • Phagocytosis / immunology*

Substances

  • Enzyme Precursors
  • Liposomes
  • Clodronic Acid
  • Complement System Proteins
  • pro-phenoloxidase
  • Catechol Oxidase