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
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1,136 citations
Cites background from "Development of a Natural Model of C..."
...Furthermore, pre-exposure of mice to sandfly saliva was found to neutralize the enhancing effects of saliv...
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583 citations
Cites methods from "Development of a Natural Model of C..."
...Parasite titrations in biphasic media for estimation of parasite loads were performed as described previously (16)....
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382 citations
Cites background or result from "Development of a Natural Model of C..."
...papatasi SGH induce the release of IL-4 at the site of inoculation (15)....
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...papatasi SGH confer protection to subsequent inoculation of parasites plus SGH (15, 18), we hypothesize that this immunity is not due to neutralization of salivary immunomodulators— such as adenosine—but rather to the modification of the parasite inoculation site due to a cell-mediated reaction with salivary gland antigens....
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...Having proposed that immunity to sand fly saliva may confer protection to subsequent Leishmania infection (15, 18), we proceeded to (a) characterize the main proteins in the salivary glands of the sand fly P....
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...We previously suggested that the exacerbating effect of SGH was mediated by an early release of IL-4 at the inoculation site (15)....
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...For example, in a previous work, the release of IL-4 was neutralized by antibodies against SGH in presensitized mice, a result correlating with protection against infection (15)....
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377 citations
Cites background or methods from "Development of a Natural Model of C..."
...The dermal cells were identified by characteristic size (forward scatter) and granulosity (side scatter) combined with two-color analysis, as previously described ( 11 )....
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...The epidermal cells were recovered as previously described ( 11 ) with modifications; briefly, the ventral and dorsal ear sheets were separated and transferred dermal side down on DMEM-penicillin/streptomycin with 0.5% trypsin (U.S....
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...Cultures were incubated at 37°C in 5% CO 2. Supernatant fluids were harvested at 24 and 48 h and were assayed for IL-4 and IFN-g, respectively, by ELISA as previously described ( 11 )....
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...The ear dermis was chosen as the inoculation site because, in addition to being a common transmission site in rodent reservoirs, it offers the advantage that all the dynamic events occurring at the site of infection as well as the interconnected compartments of the epidermis and draining lymph node can be carefully monitored ( 11 , 12)....
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...We previously established a model of natural infection that focused on the exacerbating effects of vector saliva on lesion development in a dermal site ( 11 )....
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371 citations
Cites background from "Development of a Natural Model of C..."
...mice [39] did not result in detectable changes in the monocyte...
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References
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"Development of a Natural Model of C..." refers background in this paper
...E xperimental models of leishmaniasis have only rarely attempted to reproduce the biology of natural transmission, including a consideration of ( a ) dose—sand flies inoculate low numbers of parasites, variably estimated at 10–1,000 metacyclic promastigotes (1); ( b ) saliva—parasites are coinoculated with small amounts of sand fly saliva that contain antihemostatic (2) and potentially immunomodulatory (3, 4) molecules that facilitate blood feeding; and ( c ) site of inoculation—infection is initiated in the skin, which is organized as specialized dermal and epidermal compartments containing unique cells such as keratinocytes, dendritic epidermal T cells (DETC), 1 and Langerhans’ cells that enable it to deal with the hostile external environment to which it is frequently exposed (5)....
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...Blood sucking arthropods, including infected sand flies capable of egesting Leishmania, will salivate into the skin in order to locate blood and maintain its flow during ingestion (2)....
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