RESUMO
African trypanosomes are protected by a densely packed surface monolayer of variant surface glycoprotein (VSG). A haptoglobin-hemoglobin receptor (HpHbR) within this VSG coat mediates heme acquisition. HpHbR is also exploited by the human host to mediate endocytosis of trypanolytic factor (TLF)1 from serum, contributing to innate immunity. Here, the crystal structure of HpHbR from Trypanosoma congolense has been solved, revealing an elongated three α-helical bundle with a small membrane distal head. To understand the receptor in the context of the VSG layer, the dimensions of Trypanosoma brucei HpHbR and VSG have been determined by small-angle X-ray scattering, revealing the receptor to be more elongated than VSG. It is, therefore, likely that the receptor protrudes above the VSG layer and unlikely that the VSG coat can prevent immunoglobulin binding to the receptor. The HpHb-binding site has been mapped by single-residue mutagenesis and surface plasmon resonance. This site is located where it is readily accessible above the VSG layer. A single HbHpR polymorphism unique to human infective T. brucei gambiense has been shown to be sufficient to reduce binding of both HpHb and TLF1, modulating ligand affinity in a delicate balancing act that allows nutrient acquisition but avoids TLF1 uptake.
Assuntos
Endocitose/imunologia , Imunidade Inata/imunologia , Receptores de Superfície Celular/imunologia , Glicoproteínas Variantes de Superfície de Trypanosoma/imunologia , Sequência de Aminoácidos , Animais , Sítios de Ligação/genética , Interações Hospedeiro-Parasita/imunologia , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genética , Espalhamento a Baixo Ângulo , Homologia de Sequência de Aminoácidos , Ressonância de Plasmônio de Superfície , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/imunologia , Trypanosoma brucei brucei/fisiologia , Trypanosoma brucei gambiense/genética , Trypanosoma brucei gambiense/imunologia , Trypanosoma brucei gambiense/fisiologia , Trypanosoma congolense/genética , Trypanosoma congolense/imunologia , Trypanosoma congolense/fisiologia , Tripanossomíase Africana/imunologia , Tripanossomíase Africana/parasitologia , Glicoproteínas Variantes de Superfície de Trypanosoma/química , Glicoproteínas Variantes de Superfície de Trypanosoma/genética , Difração de Raios XRESUMO
Background: Reindeer are becoming popular animals within petting farms. Few case reports describe the sedation of domesticated reindeer, but none describe the use of ocular local anesthetic blocks in this species. Case Description: A 9-year-old, female, Svalbard reindeer (Rangifer tarandus platyrhynchus) presenting for removal of a squamous cell carcinoma involving the third eyelid. Standing sedation was performed using initial boluses of medetomidine and butorphanol via intramuscular injection before catheter placement and maintenance with a variable rate infusion of medetomidine. Supraorbital, auriculopalpebral, infratrochlear blocks and local infiltration of the base of the third eyelid were performed using mepivacaine. Following the surgical removal of the third eyelid, atipamazole was administered intramuscularly to antagonize the effects of medetomidine. The patient recovered without complications. Conclusion: Medetomidine-butorphanol in combination with local anesthetic blocks provided a sufficient plane of sedation and analgesia for extra ocular surgery in a domesticated reindeer.