maxadilan-protein--insect and Leishmaniasis--Visceral

An historical review is given of American visceral leishmaniasis (AVL), with particular reference to the eco-epidemiology of the disease in Brazil. Following the first records of AVL in this country, in 1934, the sandfly Lutzomyia longipalpis (Lutz and Neiva, 1912) was incriminated as the principal vector. It is now generally accepted, however, that there exist a number of cryptic species under the name of Lu. longipalpis s.l. and that variations in the quantity of the vasodilatory peptide maxadilan in the saliva of flies from different populations of Lu. longipalpis s.l., may account for the variable clinical manifestations of AVL seen in different geographic regions. Distribution of AVL has been shown to extend throughout most of South and Central America, with the domestic dog serving as the principal reservoir of infection for man. However, while one hypothesis suggests that the causative parasite is Leishmania infantum, imported from Europe with the Portuguese and Spanish colonists, the demonstration of a high rate of benign, inapparent infection in foxes in Amazonian Brazil raised an opposing suggestion that the parasite is indigenous to the Americas. Recent reports of similar infections in native marsupials, and possibly rodents, tend to support this view, particularly as Lu. longipalpis is primordially a silvatic sandfly. Although effective control measures in foci of the disease will diminish the number of canine and human infections, the presence of such an enzootic in a variety of native animals will render the total eradication of AVL unlikely.

Topics: Animals; Brazil; Dogs; Ecosystem; Endemic Diseases; Female; Humans; Insect Proteins; Insect Vectors; Latin America; Leishmania donovani; Leishmaniasis, Visceral; Male; Psychodidae; Salivary Proteins and Peptides

Lutzomyia longipalpis expresses a salivary protein called maxadilan (MAX) that functions to dilate vertebrate blood vessels and thereby to facilitate the sand fly's acquisition of blood. We hypothesized that antibodies specific for one of many MAX variants would inhibit vasodilatory function of that variant. In vitro and in vivo experiments showed that antibodies against a specific MAX variant decreased vasodilatory function. More specifically, antibodies against MAX blocked vasodilation of a constricted rabbit aorta. Additionally, a strain of Lu. longipalpis, with a nearly uniform MAX genotype, obtained a larger blood meal from naive BALB/c mice compared with mice that were either immunized with a homologous MAX genotype or sensitized to bites of flies from the same strain. Those flies taking blood from mice sensitized by sand fly bites also laid significantly fewer eggs than when they took blood from naive mice. These results have potential epidemiologic importance in light of the potential use of MAX in a vaccine or as part of a diagnostic test because they imply that a uniform MAX genotype is selected against by the vertebrate host immune response and that antigenic diversity is selected for.

Topics: Animals; Antibodies; Female; Immunization; In Vitro Techniques; Insect Bites and Stings; Insect Proteins; Insect Vectors; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C; Oviposition; Psychodidae; Rabbits; Salivary Proteins and Peptides; Vasodilation

The salivary protein maxadilan (MAX) is a vasodilator and immunomodulator from the sand fly vector of the protozoan parasite Leishmania chagasi. Vaccinating BALB/c mice with sand fly salivary gland extracts or with MAX protects the host against L. major infection. Because of the potential use of MAX in an anti-Leishmania vaccine, we characterized the vertebrate host IgG response to MAX in the present study. Our immunochemical analysis indicated that antibodies to MAX were detected in BALB/c mice, as well as in pigs and humans, from a area in Nicaragua endemic for Lutzomyia longipalpis. Previous studies demonstrate that the MAX protein is polymorphic on the amino acid level. Our findings suggested that naturally occurring MAX variants were recognized specifically by the host immune system and antigenicity appeared to be associated with amino-acid sequence variability. Thus, antigenic diversity of MAX and possibly of other arthropod salivary proteins may dictate the development of vector-based vaccines(s).

Topics: Amino Acid Sequence; Animals; Antibody Specificity; Humans; Immunoglobulin G; Insect Proteins; Insect Vectors; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Psychodidae; Salivary Proteins and Peptides; Swine