Heme Peroxidase HPX15 Suppresses Midgut Immunity to Support Development.

Front Immunol

Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani, India; Department of Biotechnology, Ch. Bansi Lal University, Bhiwani, India.

Published: March 2017

AI Article Synopsis

  • The HPX15 gene is specific to the anopheline mosquito lineage and is found in 19 species, showing high amino acid identity, indicating a conserved function among these mosquitoes.
  • The AsHPX15 gene is highly expressed in the mosquito midgut and facilitates oocyst development after blood feeding, but silencing this gene significantly reduces oocyst numbers and increases an antiplasmodial response.
  • The study suggests that manipulating HPX15 may enhance mosquito immunity against malaria and pave the way for new malaria control strategies.

Article Abstract

The heme peroxidase HPX15 is an evolutionary conserved anopheline lineage-specific gene. Previously, we found that this gene is present in the genome of 19 worldwide distributed different species of mosquito and its orthologs are absent in other mosquitoes, insects, or human. In addition, 65-99% amino acid identity among these 19 orthologs permitted us to hypothesize that the functional aspects of this gene might be also conserved in different anophelines. In this study, we found that AsHPX15 gene is mainly expressed in the midgut and highly induced after uninfected or -infected blood feeding. RNA interference-mediated silencing of midgut AsHPX15 gene drastically reduced the number of developing oocysts. An antiplasmodial gene nitric oxide synthase was induced 13-fold in silenced midguts when compared to the unsilenced controls. Interestingly, the induction of antiplasmodial immunity in AsHPX15-silenced midguts is in absolute agreement with . In , AgHPX15 catalyzes the formation of a dityrosine network at luminal side of the midgut that suppresses the activation of mosquito immunity against the bolus bacteria. Thus, a low-immunity zone created by this mechanism indirectly supports development inside the midgut lumen. These indistinguishable functional behaviors and conserved homology indicates that HPX15 might be a potent target to manipulate the antiplasmodial immunity of the anopheline midgut, and it will open new frontiers in the field of malaria control.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348522PMC
http://dx.doi.org/10.3389/fimmu.2017.00249DOI Listing

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