Dissociation between vasodilation and Leishmania infection-enhancing effects of sand fly saliva and maxadilan

Castro-Sousa, Fábio; Paranhos-Silva, Moacir; Sherlock, Ítalo Rodrigues de Araújo; Paixão, Mariza S.; Pontes-de-Carvalho, Lain Carlos; dos-Santos, Washington Lc

doi:10.1590/s0074-02762001000700019

Cited by 11 publications

(5 citation statements)

References 8 publications

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“…The lack of enhancing effect of the SGL cannot be explained by anti-saliva antibody activity, since the animals were negative for that activity before the cutaneous injection of SGL. In effect, our results are in agreement with the observations that L. longipalpis SGLs with high vasodilation activity did not enhance experimental L. chagasi infection in mongrel dogs (Paranhos et al, 1993) and may vary in their ability to enhance infection in murine models of tegumentar leishmaniasis (Castro-Sousa et al, 2001;Warburg et al, 1994).…”

Section: Discussionsupporting

confidence: 91%

A follow-up of Beagle dogs intradermally infected with Leishmania chagasi in the presence or absence of sand fly saliva

Paranhos-Silva

Oliveira

Reis

et al. 2003

Veterinary Parasitology

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In this study, we compare the development of infection and/or disease in Beagle dogs intradermally infected with Leishmania chagasi, in the presence or absence of Lutzomyia longipalpis saliva, with those of intravenously infected animals. Spleen samples of all the animals inoculated with parasites had positive polymerase chain reaction tests for Leishmania DNA. Positive spleen cultures for Leishmania were detected earlier (P < or = 0.018) and were more frequent (five out of the five animals) in intravenously infected animals than in the intradermally infected animals, in presence (two out of the six animals) or absence (three out of the five animals) of salivary gland lysate of L. longipalpis. Significant increase in serum antibodies against Leishmania was observed only in the intravenously infected group (P = 0.004). In addition, dogs with infection confirmed by isolation of amastigotes or detection of parasite DNA were, nevertheless, negative for anti-Leishmania antibodies up to 5 months or more after infection. Only animals of the intravenously infected group developed progressive decreases in hematocrit (Pearson r = -0.8076, P = -0.0026) and hemoglobin (Pearson r = -0.8403, P = 0.0012) during the infection period. No significant difference in the course of infection was observed between groups of intradermally infected animals. The data presented herein confirms that the intradermal inoculation of dogs with Leishmania produces an asymptomatic form of infection. It also fails to show an advantage in using L. longipalpis saliva as an infection-enhancing agent in experimental canine leishmaniasis.

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Section: Discussionsupporting

confidence: 91%

A follow-up of Beagle dogs intradermally infected with Leishmania chagasi in the presence or absence of sand fly saliva

Paranhos-Silva

Oliveira

Reis

et al. 2003

Veterinary Parasitology

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“…This led us to consider the identity of potential exacerbation factors. Previous work has shown that co-inoculation of parasites and sand fly salivary gland homogenate by syringe can exacerbate leishmaniasis6,7, although the interpretation of these data in the context of natural transmission has been called into question1,17,18. We confirmed, as expected, the presence of saliva in the egestion medium (Supplementary Fig.…”

supporting

confidence: 87%

Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG

Rogers

Ilg

Nikolaev

et al. 2004

Nature

240

252

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Sand flies are the exclusive vectors of the protozoan parasite Leishmania1, but the mechanism of transmission by fly bite has not been determined nor incorporated into experimental models of infection. In sand flies with mature Leishmania infections the anterior midgut is blocked by a gel of parasite origin, the promastigote secretory gel (PSG)2,3. Here, we analyse for the first time the inocula from Leishmania mexicana infected Lutzomyia longipalpis sand flies. This revealed the size of the infectious dose, the underlying mechanism of parasite delivery by regurgitation, and the novel contribution made to infection by filamentous proteophosphoglycan (fPPG), a component of PSG found to accompany the parasites during transmission. Collectively, these results have important implications for understanding the relationship between parasite and its vector, the pathology of cutaneous leishmaniasis in humans and also the development of effective vaccines and drugs. These findings emphasise that to fully understand transmission of vector-borne diseases the interaction between all three participants must be considered.Leishmaniasis is a parasitic disease that currently infects some 12 million people worldwide, causing severe morbidity and mortality4. Infection is initiated by distinct life cycle stages, metacyclic promastigotes, that are introduced into the skin by fly bite along with sand fly saliva5-7. Leishmania are known to express various "virulence factors" in the sand fly, which may facilitate transmission to and infection of the mammalian host8-12. However, despite these discoveries our knowledge of parasite molecules that facilitate sand fly transmission is still limited. Furthermore, a number of key issues of transmission remain unresolved, such as the true infective dose, the mechanism of parasite delivery and the biological consequences of these upon infection. Significantly, in all Leishmania-vector combinations examined to date a gel-like plug, the parasite-derived PSG, blocks the anterior parts of the midgut coincident with the accumulation of metacyclic promastigotes2,3. An important structural component of PSG is fPPG, an unusual mucin-like glycoprotein unique to Leishmania13,14. Here we address these issues regarding transmission and reveal a novel contribution made by L. mexicana PSG to the infection process.Correspondence and requests for materials should be addressed to P. A.B. (pbates@liv.ac.uk To begin to understand the nature of the infective inoculum, the number and composition of L. mexicana parasites delivered during transmission was determined. A membrane feeding system was adapted to collect parasites egested by infected sand flies, revealing an average of 1086 parasites delivered per bite, highly enriched in metacyclic promastigotes (86-98%) ( Table 1). The only previous investigations quantitating egested parasites have been made using microcapillary forced feeding15,16. When this method was employed on L. mexicanainfected sand flies an average of 105 promastigotes were collected per...

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“…Indeed, a recent review (36) contended that "in virtually every system analyzed, arthropod saliva has in fact enhanced infection with pathogens." Nevertheless, the review also noted that this was not universal and cited several studies in which saliva was found to have little or no effect on transmission of Leishmania (7,8,25). Because Plasmodium sporozoites are the most important pathogens transmitted by arthropods, there is considerable interest in the role that mosquito saliva may play in sporozoite infectivity.…”

Section: Discussionmentioning

confidence: 99%

Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity ofPlasmodiumSporozoites Injected into Mice

2010

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Malaria infection is initiated when a female Anopheles mosquito probing for blood injects saliva, together with sporozoites, into the skin of its mammalian host. Prior studies had suggested that saliva may enhance sporozoite infectivity. Using rodent malaria models (Plasmodium berghei and P. yoelii), we were unable to show that saliva had any detectable effect on sporozoite infectivity. This is encouraging for plans to immunize humans with washed, attenuated P. falciparum sporozoites because many individuals develop cutaneous, hypersensitivity reactions to mosquito saliva after repeated exposure. If washed sporozoites have no appreciable loss of infectivity, they likely do not have decreased immunogenicity; thus, vaccinees are unlikely to develop cutaneous reactions against mosquito saliva during attempted immunization with such sporozoites. Earlier studies also suggested that repeated prior exposure to mosquito saliva reduces infectivity of sporozoites injected by mosquitoes into sensitized hosts. However, our own studies show that prior exposure of mice to saliva had no detectable effect on numbers of sporozoites delivered by infected mosquitoes, the rate of disappearance of these sporozoites from the skin or infectivity of the sporozoites. Under natural conditions, sporozoites are delivered both to individuals who may exhibit cutaneous hypersensitivity to mosquito bite and to others who may have not yet developed such reactivity. It was tempting to hypothesize that differences in responsiveness to mosquito bite by different individuals might modulate the infectivity of sporozoites delivered into a milieu of changes induced by cutaneous hypersensitivity. Our results with rodent malaria models, however, were unable to support such a hypothesis.The malaria infection is initiated when a female Anopheles mosquito probing for a blood meal injects saliva, together with sporozoites into the skin of its mammalian host (18, 39). Mosquito saliva is known to enhance the ability of the mosquito to locate a blood source and to inhibit hemostasis by any of several mechanisms. These include injection of an anticoagulant factor (34), inhibition of platelet aggregation by salivary apyrase (29) or a salivary factor that inhibits collagen-induced platelet aggregation (43), inhibition of thrombin activity (14), and vasodilation of host blood vessels (30). Arthropod saliva has been shown to enhance the infectivity of several different pathogens introduced into hosts by arthropods; these include sandfly transmission of Leishmania, tick transmission of viruses and spirochetes, and mosquito transmission of viruses (for a review, see reference 36). Enhancement of Plasmodium sporozoite infectivity by mosquito saliva has also been reported (12, 36) based on a prior study (41), but we felt that this study needed to be reassessed.In addition to these studies on the direct effect of arthropod saliva on infectivity of pathogens injected by arthropods into immunologically naive hosts, studies have also been done on the role of prior exposure...

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Dissociation between vasodilation and Leishmania infection-enhancing effects of sand fly saliva and maxadilan

Abstract: In this study, the ability of maxadilan and

Cited by 11 publications

References 8 publications

A follow-up of Beagle dogs intradermally infected with Leishmania chagasi in the presence or absence of sand fly saliva

A follow-up of Beagle dogs intradermally infected with Leishmania chagasi in the presence or absence of sand fly saliva

Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG

Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity ofPlasmodiumSporozoites Injected into Mice

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