title: Identification of antibodies to Leishmania silent information regulatory 2 (SIR2) protein homologue during canine natural infections: pathological implications.
abstract: Dogs are the domestic reservoir of zoonotic visceral Leishmaniasis caused by Leishmania infantum in the Mediterranean basin and thus constitute an important health problem in both human and veterinary medicine. Until vaccines become available, conventional measures such as epidemiological surveillance including reservoir control will be among the practical options for prevention and containment of the disease. We have recently characterised novel Leishmania sp. genes encoding parasite proteins named (LmS3a: homologous to mammalian ribosomal protein S3a; LmSIR2: homologous to the silent information regulatory 2 protein family; LimTXNPx: homologous to the peroxiredoxin family with N-terminal mitochondrial leader sequence) that may contribute to the host immune dysfunction in murine experimental Leishmaniasis. In the present study we have investigated the humoral responses against the parasite antigens in groups of L. infantum-infected dogs with different clinical status: symptomatic and asymptomatic with DTH positive or negative test. The determination of immunoglobulin (Ig) isotypes revealed high levels of total IgG in both symptomatic and asymptomatic animals when compared to IgM. Furthermore, the IgG2 appeared to be the predominant subclass of Ig present in the sera of infected animals particularly in the case of symptomatic dogs. The IgG subclass reactivity analysis revealed a broad specific recognition range of parasite recombinant antigens. Interestingly, differential profiles of IgG1 and IgG2 antibody reactivity were observed in asymptomatic and symptomatic dogs. The LmSIR2 protein was found to be a highly reactive molecule with IgG2 from most of the asymptomatic and symptomatic animals. Considering the fact that LmSIR2 secreted by the parasites can be bound and taken up by neighbouring cells, the latter could be a target for anti-LmSIR2 antibodies and this may contribute to the immunopathological alterations and host tissue damage. The implications of these observations in the pathogenesis of Leishmaniasis are discussed.
authors.affiliation: Biochemical Laboratory, Faculty of Pharmacy, University of Porto, Rua Anibal Cunha, 164, Porto, Portugal. mop62612@mail.telepac.pt
authors.forename: A
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.forename: L
authors.initials: L
authors.lastname: Cardoso
authors.forename: N
authors.initials: N
authors.lastname: Araújo
authors.forename: H
authors.initials: H
authors.lastname: Castro
authors.forename: A
authors.initials: A
authors.lastname: Tomás
authors.forename: M
authors.initials: M
authors.lastname: Rodrigues
authors.forename: M
authors.initials: M
authors.lastname: Cabral
authors.forename: B
authors.initials: B
authors.lastname: Vergnes
authors.forename: D
authors.initials: D
authors.lastname: Sereno
authors.forename: A
authors.initials: A
authors.lastname: Ouaissi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D004283:Dog Diseases / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D004285:Dogs; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000662:veterinary*; D015800:Protozoan Proteins / Q000276:immunology; D037761:Sirtuins / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015800:Protozoan Proteins; C402626:S3a-related protein, Leishmania major; D037761:Sirtuins