RESUMO
La placenta es un órgano imprescindible para llevar adelante la gestación en mamíferos domésticos. Está constituida por tejidos maternos y fetales y cumple numerosas funciones: intercambio de gases, nutrientes y excreción de productos de desecho, función inmune a nivel de tolerancia y transferencia, función endócrina sintetizando hormonas y factores de crecimiento. Existe una gran diversidad estructural en las placentas de diferentes especies animales. Las clasificaciones de mayor relevancia son la que dependen de la descripción morfológica macroscópica, basada en la distribución de las vellosidades placentarias en el corion del feto y la clasificación histológica, fundamentada en el número de capas que se interponen entre la sangre materna y la fetal, determinando la transferencia de inmunoglobulinas (Igs) a través de este órgano. El objetivo del presente trabajo es describir la estructura placentaria en diferentes especies y su impacto en la transferencia de la inmunidad materno-fetal. (AU)
The placenta is an essential organ for pregnancy in domestic mammals. It is constituted by maternal fetal tissues and fulfills numerous functions: exchange of gases, nutrients and excretion of waste products, prevents the immune system from identifying the embryo as a foreign body and synthesizes hormones and growth factors. There is great structural diversity in placentas of different animal species, and those can be classified in different ways. The most relevant is the macroscopic morphological classification, which is based on the distribution of the placental villi in the corium of the fetus, and the histological, that relies on the number of layers between maternal and fetal blood, determining if there is immunoglobulin (Ig) transfer or it is carried out through the colostrum. The objective of the work is to describe the placental structure in different species and its impact on the transfer of maternal-fetal immunity. (AU)
Assuntos
Humanos , Animais , Placenta/anatomia & histologia , Eutérios/imunologia , Imunoglobulinas , Feto , Imunidade Materno-AdquiridaRESUMO
Sirenians share with cetaceans and pinnipeds several convergent traits selected for the aquatic lifestyle. Living in water poses new challenges not only for locomotion and feeding but also for combating new pathogens, which may render the immune system one of the best tools aquatic mammals have for dealing with aquatic microbial threats. So far, only cetaceans have had their class II Major Histocompatibility Complex (MHC) organization characterized, despite the importance of MHC genes for adaptive immune responses. This study aims to characterize the organization of the marine mammal class II MHC using publicly available genomes. We located class II sequences in the genomes of one sirenian, four pinnipeds and eight cetaceans using NCBI-BLAST and reannotated the sequences using local BLAST search with exon and intron libraries. Scaffolds containing class II sequences were compared using dotplot analysis and introns were used for phylogenetic analysis. The manatee class II region shares overall synteny with other mammals, however most DR loci were translocated from the canonical location, past the extended class II region. Detailed analysis of the genomes of closely related taxa revealed that this presumed translocation is shared with all other living afrotherians. Other presumptive chromosome rearrangements in Afrotheria are the deletion of DQ loci in Afrosoricida and deletion of DP in E. telfairi. Pinnipeds share the main features of dog MHC: lack of a functional pair of DPA/DPB genes and inverted DRB locus between DQ and DO subregions. All cetaceans share the Cetartiodactyla inversion separating class II genes into two subregions: class IIa, with DR and DQ genes, and class IIb, with non-classic genes and a DRB pseudogene. These results point to three distinct and unheralded class II MHC structures in marine mammals: one canonical organization but lacking DP genes in pinnipeds; one bearing an inversion separating IIa and IIb subregions lacking DP genes found in cetaceans; and one with a translocation separating the most diverse class II gene from the MHC found in afrotherians and presumptive functional DR, DQ, and DP genes. Future functional research will reveal how these aquatic mammals cope with pathogen pressures with these divergent MHC organizations.
Assuntos
Eutérios/genética , Eutérios/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Animais , Genômica , Mamíferos , FilogeniaRESUMO
Background: In pregnancy, Plasmodium falciparum parasites express the surface antigen VAR2CSA, which mediates adherence of red blood cells to chondroitin sulfate A (CSA) in the placenta. VAR2CSA antibodies are generally acquired during infection in pregnancy and are associated with protection from placental malaria. We observed previously that men and children in Colombia also had antibodies to VAR2CSA, but the origin of these antibodies was unknown. Here, we tested whether infection with Plasmodium vivax is an alternative mechanism of acquisition of VAR2CSA antibodies. Methods: We analyzed sera from nonpregnant Colombians and Brazilians exposed to P. vivax and monoclonal antibodies raised against P. vivax Duffy binding protein (PvDBP). Cross-reactivity to VAR2CSA was characterized by enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry, and antibodies were tested for inhibition of parasite binding to CSA. Results: Over 50% of individuals had antibodies that recognized VAR2CSA. Affinity-purified PvDBP human antibodies and a PvDBP monoclonal antibody recognized VAR2CSA, showing that PvDBP can give rise to cross-reactive antibodies. Importantly, the monoclonal antibody inhibited parasite binding to CSA, which is the primary in vitro correlate of protection from placental malaria. Conclusions: These data suggest that PvDBP induces antibodies that functionally recognize VAR2CSA, revealing a novel mechanism of cross-species immune recognition to falciparum malaria.