Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 302K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Belkaid, Y. Articles by Sacks, D. L. Search for Related Content PubMed PubMed Citation Articles by Belkaid, Y. Articles by Sacks, D. L. Social Bookmarking                            What's this?

Articles

Yasmine Belkaid^*, Shaden Kamhawi^*, Govind Modi^*, Jesus Valenzuela^*, Nancy Noben-Trauth, Edgar Rowton, José Ribeiro^*, and David L. Sacks^*

From the ^* Laboratory of Parasitic Diseases and the Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the Department of Entomology, Walter Reed Army Institute of Research, Washington DC 20307

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.

Key Words: Leishmania major • sand flies • saliva • skin • cytokines

Abbreviations used: DETC, dendritic epidermal T cells; DTH, delayed type hypersensitivity; SGS, salivary gland sonicate; SLA, soluble L. major antigen.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Akilov, O. E., Ustyugova, I. V., Zhi, L., Hasan, T., Wu, M. X. (2009). Enhanced Susceptibility to Leishmania Infection in Resistant Mice in the Absence of Immediate Early Response Gene X-1. J. Immunol. 183: 7994-8003 [Abstract] [Full Text]  
• Mendez, S., Traslavina, R., Hinchman, M., Huang, L., Green, P., Cynamon, M. H., Welch, J. T. (2009). The Antituberculosis Drug Pyrazinamide Affects the Course of Cutaneous Leishmaniasis In Vivo and Increases Activation of Macrophages and Dendritic Cells. Antimicrob. Agents Chemother. 53: 5114-5121 [Abstract] [Full Text]  
• Benhnini, F., Chenik, M., Laouini, D., Louzir, H., Cazenave, P. A., Dellagi, K. (2009). Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due to Leishmania major Infection in Four Inbred Mouse Strains. CVI 16: 1529-1537 [Abstract] [Full Text]  
• Carregaro, V., Valenzuela, J. G., Cunha, T. M., Verri, W. A. Jr., Grespan, R., Matsumura, G., Ribeiro, J. M. C., Elnaiem, D.-E., Silva, J. S., Cunha, F. Q. (2008). Phlebotomine salivas inhibit immune inflammation-induced neutrophil migration via an autocrine DC-derived PGE2/IL-10 sequential pathway. J. Leukoc. Biol. 84: 104-114 [Abstract] [Full Text]  
• Wheat, W. H., Pauken, K. E., Morris, R. V., Titus, R. G. (2008). Lutzomyia longipalpis Salivary Peptide Maxadilan Alters Murine Dendritic Cell Expression of CD80/86, CCR7, and Cytokine Secretion and Reprograms Dendritic Cell-Mediated Cytokine Release from Cultures Containing Allogeneic T Cells. J. Immunol. 180: 8286-8298 [Abstract] [Full Text]  
• Gomes, R., Teixeira, C., Teixeira, M. J., Oliveira, F., Menezes, M. J., Silva, C., de Oliveira, C. I., Miranda, J. C., Elnaiem, D.-E., Kamhawi, S., Valenzuela, J. G., Brodskyn, C. I. (2008). Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model. Proc. Natl. Acad. Sci. USA 105: 7845-7850 [Abstract] [Full Text]  
• Reckling, S., Divanovic, S., Karp, C. L., Wojciechowski, S., Belkaid, Y., Hildeman, D. (2008). Proapoptotic Bcl-2 Family Member Bim Promotes Persistent Infection and Limits Protective Immunity. Infect. Immun. 76: 1179-1185 [Abstract] [Full Text]  
• Gannavaram, S., Vedvyas, C., Debrabant, A. (2008). Conservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites. J. Cell Sci. 121: 99-109 [Abstract] [Full Text]  
• Nagase, H., Jones, K. M., Anderson, C. F., Noben-Trauth, N. (2007). Despite Increased CD4+Foxp3+ Cells within the Infection Site, BALB/c IL-4 Receptor-Deficient Mice Reveal CD4+Foxp3-Negative T Cells as a Source of IL-10 in Leishmania major Susceptibility. J. Immunol. 179: 2435-2444 [Abstract] [Full Text]  
• Strauss-Ayali, D., Conrad, S. M., Mosser, D. M. (2007). Monocyte subpopulations and their differentiation patterns during infection. J. Leukoc. Biol. 82: 244-252 [Abstract] [Full Text]  
• Donovan, M. J., Messmore, A. S., Scrafford, D. A., Sacks, D. L., Kamhawi, S., McDowell, M. A. (2007). Uninfected Mosquito Bites Confer Protection against Infection with Malaria Parasites. Infect. Immun. 75: 2523-2530 [Abstract] [Full Text]  
• Akilov, O. E., Kasuboski, R. E., Carter, C. R., McDowell, M. A. (2007). The role of mannose receptor during experimental leishmaniasis. J. Leukoc. Biol. 81: 1188-1196 [Abstract] [Full Text]  
• MONTEIRO, M. C., LIMA, H. C., SOUZA, A. A. A., TITUS, R. G., ROMAO, P. R. T., DE QUEIROZ CUNHA, F. (2007). EFFECT OF LUTZOMYIA LONGIPALPIS SALIVARY GLAND EXTRACTS ON LEUKOCYTE MIGRATION INDUCED BY LEISHMANIA MAJOR. Am J Trop Med Hyg 76: 88-94 [Abstract] [Full Text]  
• Caljon, G., Van Den Abbeele, J., Stijlemans, B., Coosemans, M., De Baetselier, P., Magez, S. (2006). Tsetse Fly Saliva Accelerates the Onset of Trypanosoma brucei Infection in a Mouse Model Associated with a Reduced Host Inflammatory Response. Infect. Immun. 74: 6324-6330 [Abstract] [Full Text]  
• Jacobs, N., Chen, R. A.-J., Gubser, C., Najarro, P., Smith, G. L. (2006). Intradermal immune response after infection with Vaccinia virus.. J. Gen. Virol. 87: 1157-1161 [Abstract] [Full Text]  
• Teixeira, C. R., Teixeira, M. J., Gomes, R. B. B., Santos, C. S., Andrade, B. B., Raffaele-Netto, I., Silva, J. S., Guglielmotti, A., Miranda, J. C., Barral, A., Brodskyn, C., Barral-Netto, M. (2005). Saliva from Lutzomyia longipalpis Induces CC Chemokine Ligand 2/Monocyte Chemoattractant Protein-1 Expression and Macrophage Recruitment. J. Immunol. 175: 8346-8353 [Abstract] [Full Text]  
• Rosas, L. E., Keiser, T., Barbi, J., Satoskar, A. A., Septer, A., Kaczmarek, J., Lezama-Davila, C. M., Satoskar, A. R. (2005). Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice. Int Immunol 17: 1347-1357 [Abstract] [Full Text]  
• de Moura, T. R., Novais, F. O., Oliveira, F., Clarencio, J., Noronha, A., Barral, A., Brodskyn, C., de Oliveira, C. I. (2005). Toward a Novel Experimental Model of Infection To Study American Cutaneous Leishmaniasis Caused by Leishmania braziliensis. Infect. Immun. 73: 5827-5834 [Abstract] [Full Text]  
• Iborra, S., Carrion, J., Anderson, C., Alonso, C., Sacks, D., Soto, M. (2005). Vaccination with the Leishmania infantum Acidic Ribosomal P0 Protein plus CpG Oligodeoxynucleotides Induces Protection against Cutaneous Leishmaniasis in C57BL/6 Mice but Does Not Prevent Progressive Disease in BALB/c Mice. Infect. Immun. 73: 5842-5852 [Abstract] [Full Text]  
• Tabbara, K. S., Peters, N. C., Afrin, F., Mendez, S., Bertholet, S., Belkaid, Y., Sacks, D. L. (2005). Conditions Influencing the Efficacy of Vaccination with Live Organisms against Leishmania major Infection. Infect. Immun. 73: 4714-4722 [Abstract] [Full Text]  
• Demeure, C. E., Brahimi, K., Hacini, F., Marchand, F., Peronet, R., Huerre, M., St.-Mezard, P., Nicolas, J.-F., Brey, P., Delespesse, G., Mecheri, S. (2005). Anopheles Mosquito Bites Activate Cutaneous Mast Cells Leading to a Local Inflammatory Response and Lymph Node Hyperplasia. J. Immunol. 174: 3932-3940 [Abstract] [Full Text]  
• SILVA, F., GOMES, R., PRATES, D., MIRANDA, J. C., ANDRADE, B., BARRAL-NETTO, M., BARRAL, A. (2005). INFLAMMATORY CELL INFILTRATION AND HIGH ANTIBODY PRODUCTION IN BALB/c MICE CAUSED BY NATURAL EXPOSURE TO LUTZOMYIA LONGIPALPIS BITES. Am J Trop Med Hyg 72: 94-98 [Abstract] [Full Text]  
• Mendez, S., Reckling, S. K., Piccirillo, C. A., Sacks, D., Belkaid, Y. (2004). Role for CD4+ CD25+ Regulatory T Cells in Reactivation of Persistent Leishmaniasis and Control of Concomitant Immunity. JEM 200: 201-210 [Abstract] [Full Text]  
• Uzonna, J. E., Joyce, K. L., Scott, P. (2004). Low Dose Leishmania major Promotes a Transient T Helper Cell Type 2 Response That Is Down-regulated by Interferon {gamma}-producing CD8+ T Cells. JEM 199: 1559-1566 [Abstract] [Full Text]  
• Baldwin, T., Henri, S., Curtis, J., O'Keeffe, M., Vremec, D., Shortman, K., Handman, E. (2004). Dendritic Cell Populations in Leishmania major-Infected Skin and Draining Lymph Nodes. Infect. Immun. 72: 1991-2001 [Abstract] [Full Text]  
• Norsworthy, N. B., Sun, J., Elnaiem, D., Lanzaro, G., Soong, L. (2004). Sand Fly Saliva Enhances Leishmania amazonensis Infection by Modulating Interleukin-10 Production. Infect. Immun. 72: 1240-1247 [Abstract] [Full Text]  
• Costa, D. J., Favali, C., Clarencio, J., Afonso, L., Conceicao, V., Miranda, J. C., Titus, R. G., Valenzuela, J., Barral-Netto, M., Barral, A., Brodskyn, C. I. (2004). Lutzomyia longipalpis Salivary Gland Homogenate Impairs Cytokine Production and Costimulatory Molecule Expression on Human Monocytes and Dendritic Cells. Infect. Immun. 72: 1298-1305 [Abstract] [Full Text]  
• Baldwin, T. M., Elso, C., Curtis, J., Buckingham, L., Handman, E. (2003). The Site of Leishmania major Infection Determines Disease Severity and Immune Responses. Infect. Immun. 71: 6830-6834 [Abstract] [Full Text]  
• Zhang, W.-W., Mendez, S., Ghosh, A., Myler, P., Ivens, A., Clos, J., Sacks, D. L., Matlashewski, G. (2003). Comparison of the A2 Gene Locus in Leishmania donovani and Leishmania major and Its Control over Cutaneous Infection. J. Biol. Chem. 278: 35508-35515 [Abstract] [Full Text]  
• Mendez, S., Tabbara, K., Belkaid, Y., Bertholet, S., Verthelyi, D., Klinman, D., Seder, R. A., Sacks, D. L. (2003). Coinjection with CpG-Containing Immunostimulatory Oligodeoxynucleotides Reduces the Pathogenicity of a Live Vaccine against Cutaneous Leishmaniasis but Maintains Its Potency and Durability. Infect. Immun. 71: 5121-5129 [Abstract] [Full Text]  
• Reading, P. C., Smith, G. L. (2003). A kinetic analysis of immune mediators in the lungs of mice infected with vaccinia virus and comparison with intradermal infection. J. Gen. Virol. 84: 1973-1983 [Abstract] [Full Text]  
• Iwasaki, A. (2003). The Importance of CD11b+ Dendritic Cells in CD4+ T Cell Activation In Vivo: With Help from Interleukin 1. JEM 198: 185-190 [Full Text]  
• Colmenares, M., Kima, P. E., Samoff, E., Soong, L., McMahon-Pratt, D. (2003). Perforin and Gamma Interferon Are Critical CD8+ T-Cell-Mediated Responses in Vaccine-Induced Immunity against Leishmania amazonensis Infection. Infect. Immun. 71: 3172-3182 [Abstract] [Full Text]  
• Bullen, D. V. R., Baldwin, T. M., Curtis, J. M., Alexander, W. S., Handman, E. (2003). Persistence of Lesions in Suppressor of Cytokine Signaling-1-Deficient Mice Infected with Leishmania major. J. Immunol. 170: 4267-4272 [Abstract] [Full Text]  
• Ahmed, S., Colmenares, M., Soong, L., Goldsmith-Pestana, K., Munstermann, L., Molina, R., McMahon-Pratt, D. (2003). Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis. Infect. Immun. 71: 401-410 [Abstract] [Full Text]  
• Colmenares, M., Constant, S. L., Kima, P. E., McMahon-Pratt, D. (2002). Leishmania pifanoi Pathogenesis: Selective Lack of a Local Cutaneous Response in the Absence of Circulating Antibody. Infect. Immun. 70: 6597-6605 [Abstract] [Full Text]  
• Chen, R., Fairley, J. A., Zhao, M.-L., Giudice, G. J., Zillikens, D., Diaz, L. A., Liu, Z. (2002). Macrophages, But Not T and B Lymphocytes, Are Critical for Subepidermal Blister Formation in Experimental Bullous Pemphigoid: Macrophage-Mediated Neutrophil Infiltration Depends on Mast Cell Activation. J. Immunol. 169: 3987-3992 [Abstract] [Full Text]  
• Belkaid, Y., Von Stebut, E., Mendez, S., Lira, R., Caler, E., Bertholet, S., Udey, M. C., Sacks, D. (2002). CD8+ T Cells Are Required for Primary Immunity in C57BL/6 Mice Following Low-Dose, Intradermal Challenge with Leishmania major. J. Immunol. 168: 3992-4000 [Abstract] [Full Text]  
• Belkaid, Y., Hoffmann, K. F., Mendez, S., Kamhawi, S., Udey, M. C., Wynn, T. A., Sacks, D. L. (2001). The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti-IL-10 Receptor Antibody for Sterile Cure. JEM 194: 1497-1506 [Abstract] [Full Text]  
• Morris, R. V., Shoemaker, C. B., David, J. R., Lanzaro, G. C., Titus, R. G. (2001). Sandfly Maxadilan Exacerbates Infection with Leishmania major and Vaccinating Against It Protects Against L. major Infection. J. Immunol. 167: 5226-5230 [Abstract] [Full Text]  
• Valenzuela, J. G., Belkaid, Y., Garfield, M. K., Mendez, S., Kamhawi, S., Rowton, E. D., Sacks, D. L., Ribeiro, J. M.C. (2001). Toward a Defined Anti-Leishmania Vaccine Targeting Vector Antigens: Characterization of a Protective Salivary Protein. JEM 194: 331-342 [Abstract] [Full Text]  
• Mendez, S., Gurunathan, S., Kamhawi, S., Belkaid, Y., Moga, M. A., Skeiky, Y. A. W., Campos-Neto, A., Reed, S., Seder, R. A., Sacks, D. (2001). The Potency and Durability of DNA- and Protein-Based Vaccines Against Leishmania major Evaluated Using Low-Dose, Intradermal Challenge. J. Immunol. 166: 5122-5128 [Abstract] [Full Text]  
• Nicolas, L., Sidjanski, S., Colle, J.-H., Milon, G. (2000). Leishmania major Reaches Distant Cutaneous Sites Where It Persists Transiently while Persisting Durably in the Primary Dermal Site and Its Draining Lymph Node: a Study with Laboratory Mice. Infect. Immun. 68: 6561-6566 [Abstract] [Full Text]  
• Kamhawi, S., Belkaid, Y., Modi, G., Rowton, E., Sacks, D. (2000). Protection Against Cutaneous Leishmaniasis Resulting from Bites of Uninfected Sand Flies. Science 290: 1351-1354 [Abstract] [Full Text]  
• Sato, N., Ahuja, S. K., Quinones, M., Kostecki, V., Reddick, R. L., Melby, P. C., Kuziel, W. A., Ahuja, S. S. (2000). Cc Chemokine Receptor (Ccr)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-Inducing Dendritic Cells: Absence of Ccr2 Shifts the Leishmania major-Resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation. JEM 192: 205-218 [Abstract] [Full Text]  
• Belkaid, Y., Mendez, S., Lira, R., Kadambi, N., Milon, G., Sacks, D. (2000). A Natural Model of Leishmania major Infection Reveals a Prolonged ""Silent"" Phase of Parasite Amplification in the Skin Before the Onset of Lesion Formation and Immunity. J. Immunol. 165: 969-977 [Abstract] [Full Text]  
• Belkaid, Y., Valenzuela, J. G., Kamhawi, S., Rowton, E., Sacks, D. L., Ribeiro, J. M. C. (2000). Delayed-type hypersensitivity to Phlebotomus papatasi sand fly bite: An adaptive response induced by the fly?. Proc. Natl. Acad. Sci. USA 97: 6704-6709 [Abstract] [Full Text]  
• Charlab, R., Valenzuela, J. G., Rowton, E. D., Ribeiro, J. M. C. (1999). Toward an understanding of the biochemical and pharmacological complexity of the saliva of a hematophagous sand fly Lutzomyia longipalpis. Proc. Natl. Acad. Sci. USA 96: 15155-15160 [Abstract] [Full Text]  
• Heinzel, F. P., Maier, R. A. Jr. (1999). Interleukin-4-Independent Acceleration of Cutaneous Leishmaniasis in Susceptible BALB/c Mice following Treatment with Anti-CTLA4 Antibody. Infect. Immun. 67: 6454-6460 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS