Abstract
A vertebrate host becomes infected with Leishmania major when the sand fly vector injects parasites into skin along with saliva. Previous studies showed that salivary gland lysate of the New World sand fly Lutzomyia longipalpis markedly enhanced L. major infection in CBA mice. However, L. major is an Old World parasite transmitted in nature by the Old World sand fly Phlebotomus papatasi. Here we examine the ability of P. papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L. major. In addition, we examine the effects of salivary gland lysate on the immune response to L. major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous lesions. We found that P. papatasi salivary gland lysate dramatically exacerbated lesion development in disease-resistant CBA mice. This exacerbation of disease correlated with inhibition of the production of Thl cytokines and associated factors (IFN-gamma, IL-12, and inducible nitric oxide synthase), but with enhancement of the Th2 cytokine IL-4, whereas no changes in the levels of IL-10 and TGF-beta were noted. Importantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L. major.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Down-Regulation / immunology*
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Female
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interferon-gamma / genetics
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Interleukin-10 / biosynthesis
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Interleukin-10 / genetics
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Interleukin-12 / antagonists & inhibitors
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Interleukin-12 / biosynthesis
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Interleukin-12 / genetics
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Interleukin-4 / biosynthesis
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Interleukin-4 / genetics
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Leishmania major / immunology*
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Leishmaniasis, Cutaneous / immunology*
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Leishmaniasis, Cutaneous / parasitology
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Leishmaniasis, Cutaneous / pathology
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Lymph Nodes / enzymology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Mice
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Mice, Inbred CBA
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Phlebotomus / immunology*
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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Salivary Glands / chemistry
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Salivary Glands / immunology*
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Transforming Growth Factor beta / biosynthesis
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Transforming Growth Factor beta / genetics
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Up-Regulation / immunology*
Substances
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RNA, Messenger
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Transforming Growth Factor beta
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Interleukin-10
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Interleukin-12
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Interleukin-4
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Interferon-gamma
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse