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This parasite-related difference could result from the activity of an<jats:italic>L. amazonensis<\/jats:italic>-specific virulence factor. In agreement with this hypothesis, it is shown here that the intravenous injection of BALB\/c mice with<jats:italic>L. amazonensis<\/jats:italic>amastigote extract (<jats:italic>La<\/jats:italic>E) but not the<jats:italic>L. braziliensis<\/jats:italic>extract confers susceptibility to<jats:italic>L. braziliensis<\/jats:italic>infection. This effect was associated with high circulating levels of IgG1 anti-<jats:italic>L. amazonensis<\/jats:italic>antibodies and with an increase in interleukin-4 (IL-4) production and a decrease in gamma interferon production by draining lymph node cells. Moreover, the effect was absent in IL-4-knockout mice. The biological activity in the<jats:italic>La<\/jats:italic>E was not mediated by amphiphilic molecules and was inhibited by pretreatment of the extract with irreversible serine protease inhibitors. These findings indicate that the<jats:italic>La<\/jats:italic>E contains a virulence-related factor that (i) enhances the<jats:italic>Leishmania<\/jats:italic>infection by promoting Th2-type immune responses, (ii) is not one of the immunomodulatory<jats:italic>Leishmania<\/jats:italic>molecules described so far, and (iii) is either a serine protease or has an effect that depends on that protease activity. In addition to being<jats:italic>Leishmania<\/jats:italic>species specific, the infection-enhancing activity was also shown to depend on the host genetic makeup, as<jats:italic>La<\/jats:italic>E injections did not affect the susceptibility of C57BL\/6 mice to<jats:italic>L. braziliensis<\/jats:italic>infection. The identification of<jats:italic>Leishmania<\/jats:italic>molecules with infection-enhancing activity could be important for the development of a vaccine, since the up- or downmodulation of the immune response against a virulence factor could well contribute to controlling the infection.<\/jats:p>","DOI":"10.1128\/iai.00309-10","type":"journal-article","created":{"date-parts":[[2010,12,21]],"date-time":"2010-12-21T04:53:02Z","timestamp":1292907182000},"page":"1236-1243","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Enhancement of Experimental Cutaneous Leishmaniasis by<i>Leishmania<\/i>Molecules Is Dependent on Interleukin-4, Serine Protease\/Esterase Activity, and Parasite and Host Genetic Backgrounds"],"prefix":"10.1128","volume":"79","author":[{"given":"Virgi\u0301nia M. 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