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

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.

Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

“…A number of reports using animal models have shown that mice pre-exposed to phlebotomine saliva, or some of its components, are protected against Leishmania infection in vivo [8,[11][12][13][14][15], thus suggesting that salivary proteins could be used as targets for vaccination against leishmaniasis [16,17]. However, the anti-saliva IR as well as its possible implications on Leishmania infection following exposure to sand flies in humans have not been fully characterized.…”

Effect of salivary gland extract ofLeishmania vector,Lutzomyia longipalpis, on leukocyte migration in OVA-induced immune peritonitis

“…In addition to increasing the hemorrhagic pool where sand flies feed [8,14], salivary components also induce host immunosuppression, which is fundamental for the establishment of Leishmania infection [10,[15][16][17][18][19] production and antigen presentation by infected macrophages [20][21][22]. Furthermore, they inhibit Th1 induction, enhancing the Th2-type response with an increase of IL-4 and IL-10 in the infection [23][24][25]. A predominance of the Th1 response has been reported in several inflammatory diseases, including rheumatoid arthritis, Crohn's disease, glomerulonephritis, and immune vasculitis [26][27][28][29].…”

“…Salivary immunosuppressive components inhibit nitric oxide and hydrogen peroxide production and antigen presentation by infected macrophages [20][21][22]. Furthermore, they inhibit Th1 induction, enhancing the Th2-type response with an increase of IL-4 and IL-10 in the infection [23][24][25].…”

The languages of parasite communication

“…Replication occurs within a parasitopherous vacuole and culminates in the release of amastigotes that can also invade macrophages and undergo further cycles of replication. Both insect-and parasite-derived components enhance the replication of transmitted parasites [34,[46][47][48]. Two biological activities have been attributed to filamentous proteophosphoglycan, a major component of PSG.…”