scholarly journals Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis

2003 ◽  
Vol 71 (1) ◽  
pp. 401-410 ◽  
Author(s):  
Saeed Ahmed ◽  
M. Colmenares ◽  
L. Soong ◽  
K. Goldsmith-Pestana ◽  
L. Munstermann ◽  
...  
Keyword(s):  
Lymph Node ◽  
Visceral Leishmaniasis ◽  
Murine Model ◽  
Lymphoid Tissue ◽  
Parasite Burden ◽  
Parasite Clearance ◽  
Interleukin 4 ◽  
Infection Model ◽  
Course Of Disease ◽  
Draining Lymph Node

ABSTRACT The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated with a pattern of parasite clearance with time postinfection in the liver and skin; in contrast, parasite persistence and expansion was observed in lymphoid tissue (spleen and draining lymph node). The course of disease found appears to be similar to those reported for subclinical canine and human visceral leishmaniasis. Clearance of parasites from the skin was correlated with an inflammatory response and the infiltration and activation of CD4+ and CD8+ T cells. In contrast, in lymphoid tissue (lymph node or spleen), the production of Th1/Th2 cytokines (interleukin-4 [IL-4], IL-10, and gamma interferon) appeared to correlate with parasite burden and pathogenesis. In vaccination experiments employing the Leishmania infantum D-13 (p80) antigen, significantly higher levels of protection were found with the intradermal murine model (29 to 7,500-fold more than naive controls) than were found with a low-dose intravenous infection model (9 to 173-fold). Thus, this model should prove useful for further investigation of disease pathogenesis as well as vaccine studies of visceral leishmaniasis.

scholarly journals Heterologous Prime-Boost Vaccination with the LACK Antigen Protects against Murine Visceral Leishmaniasis

2005 ◽  
Vol 73 (8) ◽  
pp. 5286-5289 ◽  
Author(s):  
Blaise Dondji ◽  
Eva Pérez-Jimenez ◽  
Karen Goldsmith-Pestana ◽  
Mariano Esteban ◽  
Diane McMahon-Pratt
Keyword(s):  
Visceral Leishmaniasis ◽  
Vaccinia Virus ◽  
Parasite Burden ◽  
Infection Model ◽  
Necrosis Factor Alpha ◽  
Boost Vaccination ◽  
Fold Reduction ◽  
Vaccinia Viruses ◽  
Draining Lymph Node ◽  
Factor Alpha

ABSTRACT This study reports the efficacy of a heterologous prime-boost vaccination using DNA and vaccinia viruses (Western Reserve [WR] virus and modified [attenuated] vaccinia virus Ankara [MVA]) expressing the LACK antigen (Leishmania homologue of receptors for activated C kinase) and an intradermal murine infection model employing Leishmania infantum. At 1 month postinfection, vaccinated mice showed high levels of protection in the draining lymph node (240-fold reduction in parasite burden) coupled with significant levels of gamma interferon (20 to 200 ng/ml) and tumor necrosis factor alpha/lymphotoxin (8 to 134 pg/ml). Significant but lower levels of protection (6- to 30-fold) were observed in the spleen and liver. Comparable levels of protection were found for mice boosted with either LACK-WR or LACK-MVA, supporting the use of an attenuated vaccinia virus-based vaccine against human visceral leishmaniasis.

scholarly journals Obesity impairs resistance to Leishmania major infection in C57BL/6 mice

2018 ◽  
Author(s):  
Franciele Carolina Silva ◽  
Vinicius Dantas Martins ◽  
Felipe Caixeta ◽  
Matheus Batista Carneiro ◽  
Graziele Ribeiro Goes ◽  
...  
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Public Health Problem ◽  
Obese Mice ◽  
Obese People ◽  
Diet Induced Obesity ◽  
Draining Lymph Node

AbstractAn association between increased susceptibility to infectious diseases and obesity has been described as a result of impaired immunity in obese individuals. It is not clear whether a similar linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity in the immune response to cutaneous L. major infection, we studied the ability of C57BL/6 mice submitted to a high fat and sugar diet to control leishmaniasis. Mice with diet-induced obesity presented thicker lesions with higher parasite burden and more inflammatory infiltrate in the infected ear when infected with L. major. We observe no difference in IFN-γ or IL-4 production by draining lymph node cells between control and obese mice, but obese mice presented higher production of IgG1 and IL-17. A higher percentage of in vitro-infected peritoneal macrophages was found when these cells were obtained from obese mice when compared to lean mice. In vitro stimulation of macrophages with IL-17 decreased the capacity of cells from control mice to kill the parasite. Moreover, macrophages from obese mice presented higher arginase activity. Together our results indicate that diet-induced obesity impairs resistance to L. major in C57BL/6 mice without affecting the development of Th1 response.Author SummaryThe obesity is a public health problem and it is reaching extraordinary numbers in the world and others diseases are being involved and aggravated as consequence of obesity. What we know is that some diseases are more severe in obese people than in normal people. We did not know how obesity changes the profile of immune response to infectious agents, leading to the more severe diseases. That‘s why we decided to investigate how obese mice lead with Leishmania major infection. Leishmaniasis is a protozoa parasite infection considered a neglected disease. To try our hypothesis we gave a hipercaloric diet to induce obesity in C57BL/6 mice. After that, we injected L. major in the mice ear and followed the lesion for 8 weeks. We observed a ticker lesion and the cells from draining lymph node from obese mice produced more IL-17 than cells from normal mice. We also infected in vitro, macrophages from obese mice and stimulated the cells with IL-17, and we observed that the macrophages from obese mice are more infected by the L. major and it is worst in the presence of IL-17. Our results suggest that diet induced obesity decrease the resistance to infection.

scholarly journals Altering the Cellular Location of an Antigen Expressed by a DNA-Based Vaccine Modulates the Immune Response

1999 ◽  
Vol 73 (12) ◽  
pp. 10214-10223 ◽  
Author(s):  
P. J. Lewis ◽  
S. van Drunen Littel-van den Hurk ◽  
L. A. Babiuk
Keyword(s):  
Lymph Node ◽  
Immune Responses ◽  
Dna Vaccines ◽  
Interleukin 4 ◽  
Cell Mediated Immunity ◽  
Bovine Herpesvirus 1 ◽  
Draining Lymph Node ◽  
Herpesvirus 1 ◽  
Draining Lymph Nodes ◽  
Node Immunization

ABSTRACT The potential for DNA vaccines encoding mutated versions of the same antigen to modulate immune responses in C3H/HeN mice was investigated. We created expression plasmids that encoded several versions of glycoprotein D (gD) from bovine herpesvirus 1, including authentic membrane-anchored glycoprotein (pSLRSV.AgD), a secreted glycoprotein (pSLRSV.SgD), and an intracellular protein (pSLRSV.CgD). Immunization of an inbred strain of mice with these plasmids resulted in highly efficacious and long-lasting humoral and cell-mediated immunity. We also demonstrated that the cell compartment in which plasmid-encoded gD was expressed caused a deviation in the serum immunoglobulin (Ig) isotype profile as well as the predominant cytokines secreted from the draining lymph node. Immunization of C3H/HeN mice with DNA vaccines encoding cell-associated forms of gD resulted in a predominance of serum IgG2a and gamma interferon-secreting cells within the spleens and draining lymph nodes. In contrast, mice immunized with a secreted form of this same antigen displayed immune responses characterized by greater levels of interleukin 4 in the draining lymph node and IgG1 as the predominant serum isotype. We also showed evidence of compartmentalization of distinct immune responses within different lymphoid organs.

scholarly journals PREPARATION AND CHARACTERIZATION OF ANDROGRAPHOLIDE NANOPARTICLES FOR VISCERAL LEISHMANIASIS CHEMOTHERAPY: IN VITRO AND IN VIVO EVALUATIONS

2016 ◽  
Vol 8 (12) ◽  
pp. 102
Author(s):  
Pallab Ghosh ◽  
Subhasish Mondal ◽  
Tanmoy Bera
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Parasite Burden ◽  
Plga Nanoparticles ◽  
Antileishmanial Activity ◽  
Infection Model ◽  
Vitamin E Tpgs ◽  
Polyethylene Glycol 1000

<p><strong>Objective: </strong>To overcome low physiological solubility, poor bioavailability, the short plasma half-life of andrographolide (AG), a delivery system based on poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were developed to increase the efficiency of AG against visceral leishmaniasis (VL).<strong> </strong></p><p><strong>Methods: </strong>Andrographolide-PLGA nanoparticles (AGnp) were prepared with Pgp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) by emulsion solvent evaporation method and characterized. Antileishmanial activity was evaluated using<em> in vitro</em> and<em> in vivo</em> VL infection model. <strong></strong></p><p><strong>Results: </strong>The particle size of AGnp was found to be171.4±11.5 nm with an encapsulation efficiency of 81%. The AGnp reduced AG cellular toxicity, retained it's<em> in vitro</em> antileishmanial activity and lead to a reduction (99.9%) of parasite burden in the <em>Leishmania donovani</em> infected spleen and liver. AGnp was more active in infected mice liver at low dose than in spleen. Therapeutic indexes (TI) were 6.9-fold greater in AG and 68-fold in AGnp compared to amphotericin B (AmB) when evaluated in <em>L. donovani</em> infected spleen.<strong> </strong></p><p><strong>Conclusion: </strong>Incorporation of AG in PLGA nanoparticles, provided controlled and improved <em>in vivo</em> performance against VL</p>

scholarly journals 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

2000 ◽  
Vol 68 (12) ◽  
pp. 6561-6566 ◽  
Author(s):  
Luc Nicolas ◽  
Sacha Sidjanski ◽  
Jean-Hervé Colle ◽  
Geneviève Milon
Keyword(s):  
Lymph Node ◽  
Leishmania Major ◽  
Early Time ◽  
Parasite Load ◽  
Interleukin 4 ◽  
Complex Process ◽  
Metacyclic Promastigotes ◽  
Draining Lymph Node ◽  
Oxide Synthase ◽  
Femoral Bone Marrow

ABSTRACT So far, studies of Leishmania persistence in mice have used injections of parasites administered either intravenously in the tail vein or subcutaneously in the footpad. These routes poorly reflect the natural conditions when the sandfly delivers metacyclic promastigotes intradermally. In this study B10D2 and BALB/c mice were inoculated within the ear dermis with 104 Leishmania major metacyclic promastigotes. The parasite load was monitored by quantitative PCR in different tissues from the dermal inoculation site to distant tissues. The two sites of multiplication and persistence of parasites were the site of L. majorinoculation and the draining lymph node (DLN), with a different pattern in the two mouse inbred lines. These two organs were the only sites harboring parasites 12 months postinoculation, with the DLN of BALB/c mice harboring around 107 parasites, a stable load from months 3 to 12. In these two sites, 8 and 12 months after inoculation, interleukin 4 (IL-4), gamma interferon, and inducible nitric oxide synthase transcripts parallel the parasite load while IL-10 transcript levels remain high. In addition, at early time points until month 3, parasite DNA was also detected in distant tissues such as the contralateral noninoculated ear or the tail skin, indicating that blood was at least transiently disseminating the parasites. In contrast,L. major DNA in liver, spleen, and femoral bone marrow remained sporadic in mice of both lines. This study is discussed within the framework of Leishmania transmission from the vertebrate host to the sandfly vector, a complex process still poorly understood.

scholarly journals Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo

The Analyst ◽  
2017 ◽  
Vol 142 (4) ◽  
pp. 649-659 ◽  
Author(s):  
Ashley E. Ross ◽  
Maura C. Belanger ◽  
Jacob F. Woodroof ◽  
Rebecca R. Pompano
Keyword(s):  
Lymph Node ◽  
Targeted Delivery ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Tissue Slices ◽  
Microfluidic Platform ◽  
Spatially Resolved ◽  
Local Stimulation ◽  
Stimulation Of

We present the first microfluidic platform for local stimulation of lymph node tissue slices and demonstrate targeted delivery of a model therapeutic.

scholarly journals Experimental Evaluation of Second-Line Oral Treatments of Visceral Leishmaniasis Caused by Leishmania infantum

1999 ◽  
Vol 43 (1) ◽  
pp. 172-174 ◽  
Author(s):  
Jean-Pierre Gangneux ◽  
Michael Dullin ◽  
Annie Sulahian ◽  
Yves Jean-Francois Garin ◽  
Francis Derouin
Keyword(s):  
Visceral Leishmaniasis ◽  
Murine Model ◽  
Experimental Evaluation ◽  
Leishmania Infantum ◽  
Parasite Load ◽  
Second Line ◽  
Meglumine Antimoniate ◽  
Marked Activity

ABSTRACT In a murine model of Leishmania infantum visceral leishmaniasis, metronidazole, ketoconazole, fluconazole, itraconazole, and terbinafine were less effective than antimonial agents in reducing hepatic parasite load. Ketoconazole potentiated the effect of meglumine antimoniate reference therapy through its marked activity against spleen infection.

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