Development of a Natural Model of Cutaneous Leishmaniasis: Powerful Effects of Vector Saliva and Saliva Preexposure on the Long-Term Outcome of Leishmania major Infection in the Mouse Ear Dermis
Yasmine Belkaid,Shaden Kamhawi,Govind B. Modi,Jesus G. Valenzuela,Nancy Noben-Trauth,Edgar Rowton,José M. C. Ribeiro,David L. Sacks +7 more
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TLDR
The studies reveal a dramatic exacerbating effect of SGS on lesion development in the dermal site, and a complete abrogation of this effect in mice preexposed to salivary components, the first to suggest that for individuals at risk of vector-borne infections, history of exposure to vector saliva might influence the outcome of Exposure to transmitted parasites.Abstract:
We have developed a model of cutaneous leishmaniasis due to Leishmania major that seeks to mimic the natural conditions of infection. 1,000 metacyclic promastigotes were coinoculated with a salivary gland sonicate (SGS) obtained from a natural vector, Phlebotomus papatasii, into the ear dermis of naive mice or of mice preexposed to SGS. The studies reveal a dramatic exacerbating effect of SGS on lesion development in the dermal site, and a complete abrogation of this effect in mice preexposed to salivary components. In both BALB/c and C57Bl/6 (B/6) mice, the dermal lesions appeared earlier, were more destructive, and contained greater numbers of parasites after infection in the presence of SGS. Furthermore, coinoculation of SGS converted B/6 mice into a nonhealing phenotype. No effect of SGS was seen in either IL-4- deficient or in SCID mice. Disease exacerbation in both BALB/c and B/6 mice was associated with an early (6 h) increase in the frequency of epidermal cells producing type 2 cytokines. SGS did not elicit type 2 cytokines in the epidermis of mice previously injected with SGS. These mice made antisaliva antibodies that were able to neutralize the ability of SGS to enhance infection and to elicit IL-4 and IL-5 responses in the epidermis. These results are the first to suggest that for individuals at risk of vector-borne infections, history of exposure to vector saliva might influence the outcome of exposure to transmitted parasites.read more
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Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice.
TL;DR: The data demonstrate that the mechanism behind leishmanization with TLR agonists may be very different depending upon the immunological background of the host, and needs to be taken into account for the rational development of successful vaccines against the disease.
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Characterization of the early inflammatory infiltrate at the feeding site of infected sand flies in mice protected from vector-transmitted Leishmania major by exposure to uninfected bites.
Clarissa Teixeira,Regis Gomes,Regis Gomes,Fabiano Oliveira,Claudio Meneses,Dana C. Gilmore,Dia-Eldin A. Elnaiem,Jesus G. Valenzuela,Shaden Kamhawi +8 more
TL;DR: It is proposed that the enhanced recruitment of Gr+ monocytes, NK cells and CD4 Th1 cells observed at the bite site of exposed mice creates an inhospitable environment that counters the establishment of L. major infection.
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Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections.
TL;DR: Whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed, is explored.
Journal ArticleDOI
Differences in the Salivary Effects of Wild-Caught Versus Colonized Phlebotomus papatasi (Diptera: Psychodidae) on the Development of Zoonotic Cutaneous Leishmaniasis in BALB/c Mice
S. Ben Hadj Ahmed,S. Ben Hadj Ahmed,Ifhem Chelbi,Belhassen Kaabi,Saifedine Cherni,M. Derbali,Elyes Zhioua +6 more
TL;DR: The results suggest that when developing a sand fly saliva-based vaccine, the natural vector populations should be considered.
Journal ArticleDOI
Immunity to LuloHya and Lundep, the salivary spreading factors from Lutzomyia longipalpis, protects against Leishmania major infection.
Ines Martin-Martin,Andrezza C. Chagas,Anderson B. Guimarães-Costa,Laura Amo,Fabiano Oliveira,Ian N. Moore,Thiago DeSouza-Vieira,Elda E. Sánchez,Montamas Suntravat,Jesus G. Valenzuela,José M. C. Ribeiro,Eric Calvo +11 more
TL;DR: It is shown that two salivary enzymes from Lutzomyia longipalpis have a synergist effect that facilitates a more efficient blood meal intake and diffusion of other sialome components and suggests the inclusion of thesesalivary proteins as components for an anti-Leishmania vaccine.
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