Antigenicity of theLeishmania infantumhistones H2B and H4 during canine viscerocutaneous leishmaniasis

Abstract

SUMMARYIn this study we show that sera from dogs naturally infected with Leishmania infantum contain antibodies that specifically react against the parasite H2B and H4 histones. The Leishmania H2B and the amino-terminal region of the histone H4, expressed as fusion proteins, when confronted with sera from canine viscerocutaneous leishmaniasis (VCL) dogs, were recognized by 63% and 47%, respectively. No reactivity was detected when sera from dogs naturally infected with pathogens other than Leishmania were used. Using a collection of synthetic peptides covering the complete sequence of both proteins, we have determined that the main linear antigenic determinants are located in the amino-terminal domains of these histones. The humoral response against histones H2B and H4 induced during canine leishmaniasis was found to be specific for Leishmania histones, since no cross-reactivity of the VCL sera with mammal histones was observed. Also, a comparative study of the prevalence of antibodies among VCL sera against the four core histones of L. infantum was performed. Although a large heterogeneity of the humoral responses against these proteins was found, histones H2A and H3 seem to be more prevalent immunogens than histones H2B and H4 during canine natural leishmaniasis. The origin of the anti-histone humoral response and its possible implications in the pathogenesis of Leishmania infection are discussed.

Identification and Characterization of T Cell-Stimulating Antigens from Leishmania by CD4 T Cell Expression Cloning

“…Interestingly, humoral immune responses against histone H2b were recently reported in dogs with canine VL. Abs to histone H2b as well as other members of the histone family were detected after the dogs developed VL due to a Leishmania infantum infection (35,36). These data suggest that histone H2b is available for immune recognition not only in situations where the immune system has controlled the infection but also in situations where the parasite has evaded protective immune mechanisms.…”

Proteomic Approach for Characterization of Immunodominant Membrane-Associated 30- to 36-Kilodalton Fraction Antigens ofLeishmania infantumPromastigotes, Reacting with Sera from Mediterranean Visceral Leishmaniasis Patients

“…One drawback of serological assays with whole parasites is the existence of cross-reactivity with other pathogens, including Trypanosoma cruzi, mycobacteria, malaria parasites, or amoebae, which are coendemic with Leishmania in many parts of the world (7,51). The performance of serodiagnostic assays could be improved by using purified or recombinant leishmanial antigens, such as gp63 (40,41,56), Hsp70 (30,48), p94 (53), gp70 and p72 (24), p32 (61), rK39 (2,11), r gene B protein (rGBP) (15,31), H2A and H2B (31,57,58,59), rLACK (31), and the promastigote surface antigen 2 (rPSA-2) (18,31,37), or synthetic peptides (14,48) and antigens from promastigote-conditioned media (33).…”

Evaluation of an Enzyme-Linked Immunosorbent Assay Based on Crude Leishmania Histone Proteins for Serodiagnosis of Human Infantile Visceral Leishmaniasis

“…The subsequent characterization of histone H3, strongly recognized by CVL sera, showed that this parasite owns the most divergent histone H3 described to date (34). It was also demonstrated that the other two histones, H2B and H4, belonging to the nucleosomal core of L. infantum are recognized by CVL sera (36). In addition, antibodies against rH2A and rH2B were detected in the sera of a large group of VL patients (22,24,29).…”