The sera from individuals suffering from cutaneous leishmaniasis due toLeishmania braziliensispresent antibodies against parasitic conserved proteins, but not their human counterparts

Abstract

Summary :Sera from individuals suffering from leishmaniasis have been shown to strongly react against conserved proteins from the parasite, such as ribosomal, histones and heat-shock proteins. Some of these proteins have also been described as immunogenic in several auto-immune syndromes, and the detection of antibodies against them is considered to be indicative of disorder of the immune system. In this paper, we investigate whether there is any relationship between the recognition of some conserved proteins from Leishmania braziliensis by individuals suffering from cutaneous (CL) and mucocutaneous (MCL) leishmaniasis, and the recognition of the human homologues of these antigens found in sufferers from autoimmune diseases. Our findings reveal that the immune response generated during CL and MCL is elicited specifically by the parasitic histone H1 and Hsp70, since the CL and MCL sera do not react against their human counterparts. In addition, evidence is presented showing the specific recognition of human proteins by the autoimmune sera, showing only a weak crossreaction with the most divergent regions of the parasitic proteins. Résumé : LES SÉRUMS DE PERSONNES SOUFFRANT DE LEISHMANIOSE CUTANÉE PRÉSENTENT UNE FORTE RÉACTION CONTRE LES PROTÉINES CONSERVÉES DES PARASITES, MAIS NE RÉAGISSENT PAS CONTRE LEURS HOMOLOGUES HUMAINS Les sérums de personnes souffrant de leishmaniose présentent une forte réaction contre les protéines conservées des parasites, comme par exemple les protéines ribosomales, les histones et les protéines de choc thermique (Hsp

Comparative and systems analyses of Leishmania spp. non-coding RNAs through developmental stages

“…Several previous works demonstrated that histone, specially H2B and H4, show antigenicity activity and were recognized by antibodies (110), apart from being upregulated when treated with sodium antimony gluconate (SAG) (111). The presence of anti-H2B antibodies has been found in symptomatic visceral and cutaneous leishmaniasis patients (112,113), corroborating that histones are needed for the correct development and survival of the parasite. Additionally, this indicates that the Ld17_v01s1_485484-485505_miRNA (form L. donovani ), which co-expresses with histone H2B, may play an important role in the regulation of parasite’s development and survival in hosts by regulating histones and other proteins.…”

“…Several previous works demonstrated that histone, specially H2B and H4, show antigenicity activity and were recognized by antibodies (110), apart from being upregulated when treated with sodium antimony gluconate (SAG) (111). The presence of anti-H2B antibodies has been found in symptomatic visceral and cutaneous leishmaniasis patients (112,113), corroborating that histones are needed for the correct development and survival of the parasite.…”

“…In a recent work, demonstrated that histone H3 could be exported to the host nucleus and bind with chromatin, which would indicate that Leishmania histones not only play a role in the regulation of parasite chromatin, but are also important for the survival of the parasite in the host cells, through changes in the structure and dynamics of the host chromatin (66) . The presence of anti-H2B antibodies has been found in symptomatic visceral and cutaneous leishmaniasis patients (70,71) corroborating that histones are needed for the correct development and survival of the parasite. Additionally, this indicates that ncRNAs that coexpress with histone proteins may play an important role in the regulation of development of the parasite and survival in hosts by the regulation of histones and other proteins.Thus, we propose histone H2B and the co-expressed ncRNAs as possible markers of drug susceptibility and survival.…”

Vaccination with L. infantum chagasi Nucleosomal Histones Confers Protection against New World Cutaneous Leishmaniasis Caused by Leishmania braziliensis

“…Antibodies specific for parasite histones, obtained from dogs with visceral leishmaniasis, react against Leishmania H2A [6], H3 [7], H2B and H4 [8] but do not recognize mammalian histones. Antibodies in sera from patients with cutaneous or mucocutaneous leishmaniasisis also recognize parasite histone H1 but not the human counterpart [9]. Regarding the T cell immunogenicity of parasite histones, recombinant versions of H2B [10] or H2A [11] induced IFN-γ secretion upon stimulation of PBMCs obtained from cutaneous leishmaniasis patients.…”