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*
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Unité d’Immunophysiologie Cellulaire, Institut Pasteur, Paris, France
A model of Leishmania major infection in C57BL/6
mice has been established that combines two main features of natural
transmission: low dose (100 metacyclic promastigotes) and inoculation
into a dermal site (the ear dermis). The evolution of the dermal lesion
could be dissociated into two distinct phases. The initial "silent"
phase, lasting 4–5 wk, favored establishment of the peak load of
parasites in the dermis in the absence of lesion formation or any overt
histopathologic changes in the site. The second phase corresponds to
the development of a lesion associated with an acute infiltration of
neutrophils, macrophages, and eosinophils into the dermis and was
coincident with the killing of parasites in the site. The onset of
immunity/pathology was correlated with the appearance of cells staining
for IL-12p40 and IFN-
in the epidermal compartment, and an expansion
of T cells capable of producing IFN- in the draining lymph node.
Parasite growth was not enhanced over the first 4.5 wk in
anti-CD4-treated mice, SCID mice, or C57BL/6 mice deficient in
IL-12p40, IFN-, CD40 ligand, or inducible NO synthase. These mice
all failed to ultimately control infection in the site, but in some
cases (anti-CD4 treated, IL-12p40-/-,
CD40 ligand-/-, and SCID) high dermal
parasite loads were associated with little or no pathology. These
results extend to a natural infection model a role for Th1 cells in
both acquired resistance and lesion formation, and document the
remarkable avoidance of this response during a prolonged phase of
parasite amplification in the skin.
This article has been cited by other articles:
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S. Reckling, S. Divanovic, C. L. Karp, S. Wojciechowski, Y. Belkaid, and D. Hildeman Proapoptotic Bcl-2 Family Member Bim Promotes Persistent Infection and Limits Protective Immunity Infect. Immun., March 1, 2008; 76(3): 1179 - 1185. [Abstract] [Full Text] [PDF]
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 D. A. Scott, S. M. Hickerson, T. J. Vickers, and S. M. Beverley The Role of the Mitochondrial Glycine Cleavage Complex in the Metabolism and Virulence of the Protozoan Parasite Leishmania major J. Biol. Chem., January 4, 2008; 283(1): 155 - 165. [Abstract] [Full Text] [PDF]
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M. S. Duthie, S. T. Reece, R. Lahiri, W. Goto, V. S. Raman, J. Kaplan, G. C. Ireton, S. Bertholet, T. P. Gillis, J. L. Krahenbuhl, et al. Antigen-Specific Cellular and Humoral Responses Are Induced by Intradermal Mycobacterium leprae Infection of the Mouse Ear Infect. Immun., November 1, 2007; 75(11): 5290 - 5297. [Abstract] [Full Text] [PDF]
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I. J. Glomski, J.-P. Corre, M. Mock, and P. L. Goossens Noncapsulated Toxinogenic Bacillus anthracis Presents a Specific Growth and Dissemination Pattern in Naive and Protective Antigen-Immune Mice Infect. Immun., October 1, 2007; 75(10): 4754 - 4761. [Abstract] [Full Text] [PDF]
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 C. F. Anderson, M. Oukka, V. J. Kuchroo, and D. Sacks CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis J. Exp. Med., February 19, 2007; 204(2): 285 - 297. [Abstract] [Full Text] [PDF]
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 M. C. MONTEIRO, H. C. LIMA, A. A. A. SOUZA, R. G. TITUS, P. R. T. ROMAO, and F. DE QUEIROZ CUNHA EFFECT OF LUTZOMYIA LONGIPALPIS SALIVARY GLAND EXTRACTS ON LEUKOCYTE MIGRATION INDUCED BY LEISHMANIA MAJOR Am J Trop Med Hyg, January 1, 2007; 76(1): 88 - 94. [Abstract] [Full Text] [PDF]
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 M. Maurer, S. L. Kostka, F. Siebenhaar, K. Moelle, M. Metz, J. Knop, and E. von Stebut Skin mast cells control T cell-dependent host defense in Leishmania major infections FASEB J, December 1, 2006; 20(14): 2460 - 2467. [Abstract] [Full Text] [PDF]
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E. Yurchenko, M. Tritt, V. Hay, E. M. Shevach, Y. Belkaid, and C. A. Piccirillo CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence J. Exp. Med., October 30, 2006; 203(11): 2451 - 2460. [Abstract] [Full Text] [PDF]
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S. Bertholet, R. Goldszmid, A. Morrot, A. Debrabant, F. Afrin, C. Collazo-Custodio, M. Houde, M. Desjardins, A. Sher, and D. Sacks Leishmania Antigens Are Presented to CD8+ T Cells by a Transporter Associated with Antigen Processing-Independent Pathway In Vitro and In Vivo J. Immunol., September 15, 2006; 177(6): 3525 - 3533. [Abstract] [Full Text] [PDF]
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F. Woelbing, S. L. Kostka, K. Moelle, Y. Belkaid, C. Sunderkoetter, S. Verbeek, A. Waisman, A. P. Nigg, J. Knop, M. C. Udey, et al. Uptake of Leishmania major by dendritic cells is mediated by Fc{gamma} receptors and facilitates acquisition of protective immunity J. Exp. Med., January 23, 2006; 203(1): 177 - 188. [Abstract] [Full Text] [PDF]
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S. Bertholet, A. Debrabant, F. Afrin, E. Caler, S. Mendez, K. S. Tabbara, Y. Belkaid, and D. L. Sacks Antigen Requirements for Efficient Priming of CD8+ T Cells by Leishmania major-Infected Dendritic Cells Infect. Immun., October 1, 2005; 73(10): 6620 - 6628. [Abstract] [Full Text] [PDF]
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 L. E. Rosas, T. Keiser, J. Barbi, A. A. Satoskar, A. Septer, J. Kaczmarek, C. M. Lezama-Davila, and A. R. Satoskar Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice Int. Immunol., October 1, 2005; 17(10): 1347 - 1357. [Abstract] [Full Text] [PDF]
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T. R. de Moura, F. O. Novais, F. Oliveira, J. Clarencio, A. Noronha, A. Barral, C. Brodskyn, and C. I. de Oliveira Toward a Novel Experimental Model of Infection To Study American Cutaneous Leishmaniasis Caused by Leishmania braziliensis Infect. Immun., September 1, 2005; 73(9): 5827 - 5834. [Abstract] [Full Text] [PDF]
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K. S. Tabbara, N. C. Peters, F. Afrin, S. Mendez, S. Bertholet, Y. Belkaid, and D. L. Sacks Conditions Influencing the Efficacy of Vaccination with Live Organisms against Leishmania major Infection Infect. Immun., August 1, 2005; 73(8): 4714 - 4722. [Abstract] [Full Text] [PDF]
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J. Ji, J. Masterson, J. Sun, and L. Soong CD4+CD25+ Regulatory T Cells Restrain Pathogenic Responses during Leishmania amazonensis Infection J. Immunol., June 1, 2005; 174(11): 7147 - 7153. [Abstract] [Full Text] [PDF]
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C. F. Anderson, S. Mendez, and D. L. Sacks Nonhealing Infection despite Th1 Polarization Produced by a Strain of Leishmania major in C57BL/6 Mice J. Immunol., March 1, 2005; 174(5): 2934 - 2941. [Abstract] [Full Text] [PDF]
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 A. Kissenpfennig, S. Ait-Yahia, V. Clair-Moninot, H. Stossel, E. Badell, Y. Bordat, J. L. Pooley, T. Lang, E. Prina, I. Coste, et al. Disruption of the langerin/CD207 Gene Abolishes Birbeck Granules without a Marked Loss of Langerhans Cell Function Mol. Cell. Biol., January 1, 2005; 25(1): 88 - 99. [Abstract] [Full Text] [PDF]
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H. K. Maxion, W. Liu, M.-H. Chang, and K. A. Kelly The Infecting Dose of Chlamydia muridarum Modulates the Innate Immune Response and Ascending Infection Infect. Immun., November 1, 2004; 72(11): 6330 - 6340. [Abstract] [Full Text] [PDF]
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S. Mendez, S. K. Reckling, C. A. Piccirillo, D. Sacks, and Y. Belkaid Role for CD4+ CD25+ Regulatory T Cells in Reactivation of Persistent Leishmaniasis and Control of Concomitant Immunity J. Exp. Med., July 19, 2004; 200(2): 201 - 210. [Abstract] [Full Text] [PDF]
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T. Baldwin, S. Henri, J. Curtis, M. O'Keeffe, D. Vremec, K. Shortman, and E. Handman Dendritic Cell Populations in Leishmania major-Infected Skin and Draining Lymph Nodes Infect. Immun., April 1, 2004; 72(4): 1991 - 2001. [Abstract] [Full Text] [PDF]
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N. B. Norsworthy, J. Sun, D. Elnaiem, G. Lanzaro, and L. Soong Sand Fly Saliva Enhances Leishmania amazonensis Infection by Modulating Interleukin-10 Production Infect. Immun., March 1, 2004; 72(3): 1240 - 1247. [Abstract] [Full Text] [PDF]
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C. De Trez, M. Brait, O. Leo, T. Aebischer, F. A. Torrentera, Y. Carlier, and E. Muraille Myd88-Dependent In Vivo Maturation of Splenic Dendritic Cells Induced by Leishmania donovani and Other Leishmania Species Infect. Immun., February 1, 2004; 72(2): 824 - 832. [Abstract] [Full Text] [PDF]
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 E. Prina, S. Z. Abdi, M. Lebastard, E. Perret, N. Winter, and J.-C. Antoine Dendritic cells as host cells for the promastigote and amastigote stages of Leishmania amazonensis: the role of opsonins in parasite uptake and dendritic cell maturation J. Cell Sci., January 15, 2004; 117(2): 315 - 325. [Abstract] [Full Text] [PDF]
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T. M. Baldwin, C. Elso, J. Curtis, L. Buckingham, and E. Handman The Site of Leishmania major Infection Determines Disease Severity and Immune Responses Infect. Immun., December 1, 2003; 71(12): 6830 - 6834. [Abstract] [Full Text] [PDF]
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B. L. Kelly, D. B. Stetson, and R. M. Locksley Leishmania major LACK Antigen Is Required for Efficient Vertebrate Parasitization J. Exp. Med., December 1, 2003; 198(11): 1689 - 1698. [Abstract] [Full Text] [PDF]
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H. W. Murray, C. M. Lu, E. B. Brooks, R. E. Fichtl, J. L. DeVecchio, and F. P. Heinzel Modulation of T-Cell Costimulation as Immunotherapy or Immunochemotherapy in Experimental Visceral Leishmaniasis Infect. Immun., November 1, 2003; 71(11): 6453 - 6462. [Abstract] [Full Text] [PDF]
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S. Mendez, K. Tabbara, Y. Belkaid, S. Bertholet, D. Verthelyi, D. Klinman, R. A. Seder, and D. L. Sacks Coinjection with CpG-Containing Immunostimulatory Oligodeoxynucleotides Reduces the Pathogenicity of a Live Vaccine against Cutaneous Leishmaniasis but Maintains Its Potency and Durability Infect. Immun., September 1, 2003; 71(9): 5121 - 5129. [Abstract] [Full Text] [PDF]
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M. M. OGG, R. CARRION JR., A. C. DE CARVALHO BOTELHO, W. MAYRINK, R. CORREA-OLIVEIRA, and J. L. PATTERSON SHORT REPORT: QUANTIFICATION OF LEISHMANIAVIRUS RNA IN CLINICAL SAMPLES AND ITS POSSIBLE ROLE IN PATHOGENESIS Am J Trop Med Hyg, September 1, 2003; 69(3): 309 - 313. [Abstract] [Full Text] [PDF]
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G. F. Spath, L.-F. Lye, H. Segawa, D. L. Sacks, S. J. Turco, and S. M. Beverley Persistence Without Pathology in Phosphoglycan-Deficient Leishmania major Science, August 29, 2003; 301(5637): 1241 - 1243. [Abstract] [Full Text] [PDF]
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E. von Stebut, J. M. Ehrchen, Y. Belkaid, S. L. Kostka, K. Molle, J. Knop, C. Sunderkotter, and M. C. Udey Interleukin 1{alpha} Promotes Th1 Differentiation and Inhibits Disease Progression in Leishmania major-susceptible BALB/c Mice J. Exp. Med., July 21, 2003; 198(2): 191 - 199. [Abstract] [Full Text] [PDF]
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A. Iwasaki The Importance of CD11b+ Dendritic Cells in CD4+ T Cell Activation In Vivo: With Help from Interleukin 1 J. Exp. Med., July 21, 2003; 198(2): 185 - 190. [Full Text] [PDF]
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T. Lang, N. Courret, J.-H. Colle, G. Milon, and J.-C. Antoine The Levels and Patterns of Cytokines Produced by CD4 T Lymphocytes of BALB/c Mice Infected with Leishmania major by Inoculation into the Ear Dermis Depend on the Infectiousness and Size of the Inoculum Infect. Immun., May 1, 2003; 71(5): 2674 - 2683. [Abstract] [Full Text] [PDF]
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D. V. R. Bullen, T. M. Baldwin, J. M. Curtis, W. S. Alexander, and E. Handman Persistence of Lesions in Suppressor of Cytokine Signaling-1-Deficient Mice Infected with Leishmania major J. Immunol., April 15, 2003; 170(8): 4267 - 4272. [Abstract] [Full Text] [PDF]
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S. Ahmed, M. Colmenares, L. Soong, K. Goldsmith-Pestana, L. Munstermann, R. Molina, and D. McMahon-Pratt Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis Infect. Immun., January 1, 2003; 71(1): 401 - 410. [Abstract] [Full Text] [PDF]
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 E. von Stebut, M. Metz, G. Milon, J. Knop, and M. Maurer Early macrophage influx to sites of cutaneous granuloma formation is dependent on MIP-1alpha /beta released from neutrophils recruited by mast cell-derived TNFalpha Blood, January 1, 2003; 101(1): 210 - 215. [Abstract] [Full Text] [PDF]
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M. A. McDowell, M. Marovich, R. Lira, M. Braun, and D. Sacks Leishmania Priming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent Infect. Immun., August 1, 2002; 70(8): 3994 - 4001. [Abstract] [Full Text] [PDF]
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A. A. Chackerian, J. M. Alt, T. V. Perera, C. C. Dascher, and S. M. Behar Dissemination of Mycobacterium tuberculosis Is Influenced by Host Factors and Precedes the Initiation of T-Cell Immunity Infect. Immun., August 1, 2002; 70(8): 4501 - 4509. [Abstract] [Full Text] [PDF]
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E. Aga, D. M. Katschinski, G. van Zandbergen, H. Laufs, B. Hansen, K. Muller, W. Solbach, and T. Laskay Inhibition of the Spontaneous Apoptosis of Neutrophil Granulocytes by the Intracellular Parasite Leishmania major J. Immunol., July 15, 2002; 169(2): 898 - 905. [Abstract] [Full Text] [PDF]
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E. G. Rhee, S. Mendez, J. A. Shah, C.-y. Wu, J. R. Kirman, T. N. Turon, D. F. Davey, H. Davis, D. M. Klinman, R. N. Coler, et al. Vaccination with Heat-killed Leishmania Antigen or Recombinant Leishmanial Protein and CpG Oligodeoxynucleotides Induces Long-Term Memory CD4+and CD8+T Cell Responses and Protection Against Leishmania major Infection J. Exp. Med., June 17, 2002; 195(12): 1565 - 1573. [Abstract] [Full Text] [PDF]
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E. Bourreau, G. Prevot, J. Gardon, R. Pradinaud, H. Hasagewa, G. Milon, and P. Launois LACK-Specific CD4+ T Cells That Induce Gamma Interferon Production in Patients with Localized Cutaneous Leishmaniasis during an Early Stage of Infection Infect. Immun., June 1, 2002; 70(6): 3122 - 3129. [Abstract] [Full Text] [PDF]
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Y. Belkaid, E. Von Stebut, S. Mendez, R. Lira, E. Caler, S. Bertholet, M. C. Udey, and D. Sacks CD8+ T Cells Are Required for Primary Immunity in C57BL/6 Mice Following Low-Dose, Intradermal Challenge with Leishmania major J. Immunol., April 15, 2002; 168(8): 3992 - 4000. [Abstract] [Full Text] [PDF]
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H. L. Compton and J. P. Farrell CD28 Costimulation and Parasite Dose Combine to Influence the Susceptibility of BALB/c Mice to Infection with Leishmania major J. Immunol., February 1, 2002; 168(3): 1302 - 1308. [Abstract] [Full Text] [PDF]
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Y. Belkaid, K. F. Hoffmann, S. Mendez, S. Kamhawi, M. C. Udey, T. A. Wynn, and D. L. Sacks 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 J. Exp. Med., November 19, 2001; 194(10): 1497 - 1506. [Abstract] [Full Text] [PDF]
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U. M. Padigel, P. J. Perrin, and J. P. Farrell The Development of a Th1-Type Response and Resistance to Leishmania major Infection in the Absence of CD40-CD40L Costimulation J. Immunol., November 15, 2001; 167(10): 5874 - 5879. [Abstract] [Full Text] [PDF]
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H. Qi, V. Popov, and L. Soong Leishmania amazonensis-Dendritic Cell Interactions In Vitro and the Priming of Parasite-Specific CD4+ T Cells In Vivo J. Immunol., October 15, 2001; 167(8): 4534 - 4542. [Abstract] [Full Text] [PDF]
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J. G. Valenzuela, Y. Belkaid, M. K. Garfield, S. Mendez, S. Kamhawi, E. D. Rowton, D. L. Sacks, and J. M.C. Ribeiro Toward a Defined Anti-Leishmania Vaccine Targeting Vector Antigens: Characterization of a Protective Salivary Protein J. Exp. Med., August 6, 2001; 194(3): 331 - 342. [Abstract] [Full Text] [PDF]
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R. Nishikomori, S. Gurunathan, K. Nishikomori, and W. Strober BALB/c Mice Bearing a Transgenic IL-12 Receptor {{beta}}2 Gene Exhibit a Nonhealing Phenotype to Leishmania major Infection Despite Intact IL-12 Signaling J. Immunol., June 1, 2001; 166(11): 6776 - 6783. [Abstract] [Full Text] [PDF]
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S. Kamhawi, Y. Belkaid, G. Modi, E. Rowton, and D. Sacks Protection Against Cutaneous Leishmaniasis Resulting from Bites of Uninfected Sand Flies Science, November 17, 2000; 290(5495): 1351 - 1354. [Abstract] [Full Text]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
