title: Anopheles stephensiHeme Peroxidase HPX15 Suppresses Midgut Immunity to SupportPlasmodiumDevelopment.
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 ofAnophelesmosquito 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 thatAnopheles stephensiAsHPX15 gene is mainly expressed in the midgut and highly induced after uninfected orPlasmodium berghei-infected blood feeding. RNA interference-mediated silencing of midgut AsHPX15 gene drastically reduced the number of developingP. bergheioocysts. 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 withAnopheles gambiae. InA. gambiae, 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 supportsPlasmodiumdevelopment 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.
authors.affiliation: Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS) , Pilani , India.
authors.forename: Mithilesh
authors.initials: M
authors.lastname: Kajla
authors.affiliation: Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS) , Pilani , India.
authors.forename: Parik
authors.initials: P
authors.lastname: Kakani
authors.affiliation: Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS) , Pilani , India.
authors.forename: Tania Pal
authors.initials: TP
authors.lastname: Choudhury
authors.affiliation: Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS) , Pilani , India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS) , Pilani , India.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS) , Pilani , India.
authors.forename: Rini
authors.initials: R
authors.lastname: Dhawan
authors.affiliation: Molecular Parasitology and Vector Biology Laboratory, Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani, India; Department of Zoology, Ch. Bansi Lal University, Bhiwani, India.
authors.forename: Lalita
authors.initials: L
authors.lastname: Gupta
authors.affiliation: 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.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
keywords: Anopheles stephensi; HPX15; Plasmodium; heme peroxidase; innate immunity; midgut; mucin barrier; vectorial capacity