title: Host modulation by a parasite: how Leishmania infantum modifies the intestinal environment of Lutzomyia longipalpis to favor its development.
abstract: Some reports have described the interference of Leishmania on sand flies physiology, and such behavior most likely evolved to favor the development and transmission of the parasite. Most of these studies showed that Leishmania could modulate the level of proteases in the midgut after an infective blood meal, and decreased proteolytic activity is indeed beneficial for the development of promastigotes in the gut of sand flies. In the present study, we performed a detailed investigation of the intestinal pH in Lutzomyia longipalpis females naturally infected with Leishmania infantum and investigated the production of trypsin by these insects using different approaches. Our results allowed us to propose a mechanism by which these parasites interfere with the physiology of L. longipalpis to decrease the production of proteolytic enzymes. According to our hypothesis L. infantum promastigotes indirectly interfere with the production of trypsin by modulating the mechanism that controls the intestinal pH via the action of a yet non-identified substance released by promastigote forms inside the midgut. This substance is not an acid, whose action would be restrict on to release H+ to the medium, but is a substance that is able to interfere with midgut physiology through a mechanism involving pH control. According to our hypothesis, as the pH decreases, the proteolytic enzymes efficiency is also reduced, leading to a decline in the supply of amino acids to the enterocytes: this decline reduces the stimulus for protease production because it is regulated by the supply of amino acids, thus leading to a delay in digestion.
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Vania Cristina
authors.initials: VC
authors.lastname: Santos
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Vladimir Fazito
authors.initials: VF
authors.lastname: Vale
authors.affiliation: Institute of Biomedical Sciences, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil.
authors.forename: Sydnei Magno
authors.initials: SM
authors.lastname: Silva
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Alexandre Alves Sousa
authors.initials: AA
authors.lastname: Nascimento
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Natalia Alvim Araujo
authors.initials: NA
authors.lastname: Saab
authors.affiliation: Laboratory of Medical Entomology, Centro de Pesquisas Rene Rachou (CPqRR), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rodrigo Pedro Pinto
authors.initials: RP
authors.lastname: Soares
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marilene Suzan Marques
authors.initials: MS
authors.lastname: Michalick
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil; National Institute of Science and Technology-Molecular Entomology, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, Distrito Federal, Brazil.
authors.forename: Ricardo Nascimento
authors.initials: RN
authors.lastname: Araujo
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil; National Institute of Science and Technology-Molecular Entomology, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, Distrito Federal, Brazil.
authors.forename: Marcos Horacio
authors.initials: MH
authors.lastname: Pereira
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
authors.affiliation: Department of Parasitology, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil; National Institute of Science and Technology-Molecular Entomology, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, Distrito Federal, Brazil.
authors.forename: Nelder Figueiredo
authors.initials: NF
authors.lastname: Gontijo
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006790:Host-Parasite Interactions / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000187:drug effects / Q000201:enzymology / Q000469:parasitology*; D007891:Leishmania / Q000502:physiology*; D011576:Psychodidae / Q000469:parasitology*; D014357:Trypsin / Q000378:metabolism
chemical_list: D000596:Amino Acids; D014357:Trypsin