Bacteria- and IMD Pathway-Independent Immune Defenses against Plasmodium falciparum in Anopheles gambiae

Benjamin J. Blumberg, Stefanie Trop, Suchismita Das, George Dimopoulos

Research output: Contribution to journalArticle

Abstract

The mosquito Anopheles gambiae uses its innate immune system to control bacterial and Plasmodium infection of its midgut tissue. The activation of potent IMD pathway-mediated anti-Plasmodium falciparum defenses is dependent on the presence of the midgut microbiota, which activate this defense system upon parasite infection through a peptidoglycan recognition protein, PGRPLC. We employed transcriptomic and reverse genetic analyses to compare the P. falciparum infection-responsive transcriptomes of septic and aseptic mosquitoes and to determine whether bacteria-independent anti-Plasmodium defenses exist. Antibiotic treated aseptic mosquitoes mounted molecular immune responses representing a variety of immune functions upon P. falciparum infection. Among other immune factors, our analysis uncovered a serine protease inhibitor (SRPN7) and Clip-domain serine protease (CLIPC2) that were transcriptionally induced in the midgut upon P. falciparum infection, independent of bacteria. We also showed that SRPN7 negatively and CLIPC2 positively regulate the anti-Plasmodium defense, independently of the midgut-associated bacteria. Co-silencing assays suggested that these two genes may function together in a signaling cascade. Neither gene was regulated, nor modulated, by infection with the rodent malaria parasite Plasmodium berghei, suggesting that SRPN7 and CLIPC2 are components of a defense system with preferential activity towards P. falciparum. Further analysis using RNA interference determined that these genes do not regulate the anti-Plasmodium defense mediated by the IMD pathway, and both factors act as agonists of the endogenous midgut microbiota, further demonstrating the lack of functional relatedness between these genes and the bacteria-dependent activation of the IMD pathway. This is the first study confirming the existence of a bacteria-independent, anti-P. falciparum defense. Further exploration of this anti-Plasmodium defense will help clarify determinants of immune specificity in the mosquito, and expose potential gene and/or protein targets for malaria intervention strategies based on targeting the parasite in the mosquito vector.

Original languageEnglish (US)
Article numbere72130
JournalPLoS One
Volume8
Issue number9
DOIs
StatePublished - Sep 3 2013

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Anopheles gambiae
Plasmodium falciparum
Malaria
Plasmodium
Bacteria
midgut
Genes
Culicidae
bacteria
infection
Microbiota
serine proteinases
genes
parasites
malaria
Chemical activation
Parasites
Serine Proteinase Inhibitors
Immune system
Plasmodium berghei

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bacteria- and IMD Pathway-Independent Immune Defenses against Plasmodium falciparum in Anopheles gambiae. / Blumberg, Benjamin J.; Trop, Stefanie; Das, Suchismita; Dimopoulos, George.

In: PLoS One, Vol. 8, No. 9, e72130, 03.09.2013.

Research output: Contribution to journalArticle

Blumberg, Benjamin J. ; Trop, Stefanie ; Das, Suchismita ; Dimopoulos, George. / Bacteria- and IMD Pathway-Independent Immune Defenses against Plasmodium falciparum in Anopheles gambiae. In: PLoS One. 2013 ; Vol. 8, No. 9.
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