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
Citations
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Systemic FasL and TRAIL neutralisation reduce leishmaniasis induced skin ulceration.
Geremew Tasew,Susanne Nylén,Thorsten Lieke,Thorsten Lieke,Befekadu Lemu,Hailu Meless,Nicolas Ruffin,Dawit Wolday,Abraham Asseffa,Hideo Yagita,Sven Britton,Hannah Akuffo,Francesca Chiodi,Liv Eidsmo +13 more
TL;DR: It is suggested that therapeutic inhibition of FasL and TRAIL could limit skin pathology during cutaneous leishmaniasis, and reduce ulceration in a model of murine Leishmania infection with no effect on parasitic loads or dissemination.
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Persistence of Lesions in Suppressor of Cytokine Signaling-1-Deficient Mice Infected with Leishmania major
TL;DR: It is suggested that SOCS1 plays an important role in the regulation of appropriate inflammatory responses during the resolution of L. major infection.
Journal ArticleDOI
Interplay between parasite cysteine proteases and the host kinin system modulates microvascular leakage and macrophage infection by promastigotes of the Leishmania donovani complex
Erik Svensjö,Paulo R. Batista,Cláudia Brodskyn,Robson Amaro Augusto da Silva,Ana Paula C. A. Lima,Veronica Schmitz,Elvira M. Saraiva,João Bosco Pesquero,Marcelo A. Mori,Werner Müller-Esterl,Julio Scharfstein +10 more
TL;DR: Evidence that inflammatory macrophages treated with HOE-140 became highly susceptible to amastigote outgrowth, assessed 72 h after initial macrophage interaction, further suggests that the kinin/B2R activation pathway may critically modulate inflammation and innate immunity in visceral leishmaniasis.
Journal ArticleDOI
Prostaglandin E2/leukotriene B4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection.
Théo Araújo-Santos,Théo Araújo-Santos,Deboraci B. Prates,Deboraci B. Prates,Jaqueline França-Costa,Jaqueline França-Costa,Nívea F. Luz,Nívea F. Luz,Bruno B. Andrade,José Carlos Miranda,Cláudia Brodskyn,Cláudia Brodskyn,Cláudia Brodskyn,Aldina Barral,Aldina Barral,Aldina Barral,Patrícia T. Bozza,Valéria M. Borges,Valéria M. Borges +18 more
TL;DR: Findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE2/LTB4 axis, which may represent an important mechanism on establishment of the infection.
Journal ArticleDOI
Nucleosides from Phlebotomus papatasi salivary gland ameliorate murine collagen-induced arthritis by impairing dendritic cell functions
Vanessa Carregaro,Anderson Sá-Nunes,Thiago M. Cunha,Renata Grespan,Carlo José Freire Oliveira,Djalma S. Lima-Junior,Diego L. Costa,Waldiceu A. Verri,Cristiane M. Milanezi,Van My Pham,David D. Brand,David D. Brand,Jesus G. Valenzuela,João Santana da Silva,José M. C. Ribeiro,Fernando Q. Cunha +15 more
TL;DR: It is revealed that ADO and 5′AMP are present in pharmacological amounts in P. papatasi saliva and act preferentially on DC function, consequently reducing Th17 subset activation and suppressing the autoimmune response, plausible that these constituents might be promising therapeutic molecules to target immune inflammatory diseases.
References
More filters
Journal ArticleDOI
Recognition of Stress-Induced MHC Molecules by Intestinal Epithelial γδ T Cells
TL;DR: In this paper, the expression and recognition of a major histocompatibility complex (MHC) class I-related molecule, MICA, matches this localization, and the closely related MICB were recognized by intestinal epithelial T cells expressing diverse Vδ1 γδ TCRs.
Journal ArticleDOI
IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine Responses
Jeanne Magram,Suzanne E. Connaughton,Rajeev R. Warrier,Daisy Carvajal,Chang-You Wu,Jessica Ferrante,Colin L. Stewart,Ulla Sarmiento,Denise A. Faherty,Maurice K. Gately +9 more
TL;DR: It is indicated that IL-12 plays an essential role in regulating IFNγ production and in facilitating normal DTH responses and other phenomena associated with Th1 responses and cell-mediated immunity, i.e., IL-2 secretion and CTL generation, were not compromised in the absence of IL- 12.
Journal ArticleDOI
Natural and synthetic non-peptide antigens recognized by human γδ T cells
TL;DR: Results provide formal evidence that, in contrast to recognition of major histocompatibility complex-bound peptide antigens by αβ T cells, human γδ T cells can recognize naturally occurring small non-peptidic antIGens.
Journal ArticleDOI
Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo
David A. Ferrick,Mark D. Schrenzel,Thera Mulvania,Beryl Hsieh,Walter G. Ferlin,Heather D Lepper +5 more
TL;DR: In this article, the authors used flow cytometry to identify the presence of intracellular cytokines (cytoflow) and analyse T-cell production of IFN-gamma and IL-4 from mice infected with Listeria monocytogenes or Nippostrongylus brasiliensis.
Journal ArticleDOI
Role of saliva in blood-feeding by arthropods
TL;DR: Distribution du sang dans la peau, agregation des plaquettes et vasoconstriction, coagulation, inflammation and hemostase, immunite, role de la salive chez les arthropodes hematophages.