Treatment with cathepsin L inhibitor potentiates Th2-type immune response in Leishmania major-infected BALB/c mice

ABSTRACT Leishmanization is the inoculation of live Leishmania into the host to vaccinate against subsequent infections. This approach has been largely discontinued due to safety concerns. We have previously shown that combining CD40 ligand (CD40L) with Leishmania antigen preferentially induces a type 1 immune response and provides some protection to vaccinated mice (G. Chen, P. A. Darrah, and D. M. Mosser, Infect. Immun. 69:3255-3263, 2001). In the present study, we developed transgenic L. major organisms which express and secrete the extracellular portion of CD40L (L. major CD40LE). We hypothesized that these organisms would be less virulent but more immunogenic than wild-type organisms and therefore be more effective at leishmanization. Transgenic parasites expressing CD40L mRNA and protein were developed. BALB/c mice infected with these parasites developed significantly smaller lesions containing fewer parasites than animals infected with wild-type organisms. Infection of resistant C57BL/6 mice with low doses of transgenic parasites induced a significant amount of protection against subsequent high-dose infection with wild-type organisms. These results demonstrate that transgenic organisms expressing CD40L are less virulent than wild-type organisms while retaining full immunogenicity.

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Leishmania major: Secreted antigens of Leishmania major promastigotes shift the immune response of the C57BL/6 mice toward Th2 in vitro

Experimental Parasitology ◽

10.1016/j.exppara.2010.06.033 ◽

2011 ◽

Vol 127 (1) ◽

pp. 46-51 ◽

Cited By ~ 9

Author(s):

Parisa-alsadat Tabatabaee ◽

Mohsen Abolhassani ◽

Mehdi Mahdavi ◽

Hossein Nahrevanian ◽

Kayhan Azadmanesh

Keyword(s):

Immune Response ◽

Leishmania Major ◽

Secreted Antigens

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Leishmania Major Infection in Major Histocompatibility Complex Class II-Deficient Mice: CD8+ T Cells Do not Mediate a Protective Immune Response

Immunobiology ◽

10.1016/s0171-2985(96)80043-x ◽

1996 ◽

Vol 195 (2) ◽

pp. 243-260 ◽

Cited By ~ 27

Author(s):

Klaus Erb ◽

Christine Blank ◽

Uwe Ritter ◽

Horst Bluethmann ◽

Heidrun Moll

Keyword(s):

Immune Response ◽

T Cells ◽

Major Histocompatibility Complex ◽

Major Histocompatibility Complex Class ◽

Cd8 T Cells ◽

Leishmania Major ◽

Complex Class ◽

Major Infection ◽

Histocompatibility Complex ◽

Deficient Mice

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Modulation of the immune response of BALB/C mice against Leishmania Major by imuvert

International Journal of Immunopharmacology ◽

10.1016/s0192-0561(97)00087-8 ◽

1997 ◽

Vol 19 (8) ◽

pp. 443-449 ◽

Cited By ~ 1

Author(s):

Safa M. Taha ◽

Khaled S. Tabbara

Keyword(s):

Immune Response ◽

Leishmania Major

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

10.1101/342642 ◽

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.

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Evaluation of Immune Response against Leishmaniasis in BALB/c Mice Immunized with Cationic DOTAP/DOPE/CHOL Liposomes Containing Soluble Leishmania major Antigens

Iranian Journal of Parasitology ◽

10.18502/ijpa.v14i1.719 ◽

2019 ◽

Author(s):

Mansure HOJATIZADE ◽

Ali BADIEE ◽

Ali KHAMESIPOUR ◽

Mahmoud Reza JAAFARI

Keyword(s):

Immune Response ◽

Leishmania Major ◽

High Titer ◽

Parasite Burden ◽

Phase Iii ◽

Th2 Response ◽

Liposomal Form ◽

Lipid Film ◽

Phase Iii Clinical Trials ◽

Ifn Γ

Background: Whole killed Leishmania vaccine reached phase III clinical trials but failed to display significant efficacy in human mainly due to limited Th1 inducer adjuvant. Liposomes consisting of 1, 2-dioleoyl-3trimethylammonium-propane (DOTAP) bearing an inherent adjuvanticity and 1, 2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) is well known to intensify the efficacy of positively charged liposomes. Methods: Soluble Leishmania major antigens (SLA) encapsulated in cationic liposomes using lipid film method in 2016). BALB/c mice were immunized subcutaneously (SC), three times in a 2-wk interval, with Lip (DOTAP)-SLA+, Lip (DOTAP/DOPE)-SLA+, Lip (DOTAP/DOPE/CHO)-SLA+, Lip (DOTAP/DOPE/CHO), Lip (DOPE/CHO), SLA or HEPES buffer. At week 2 after the last booster injection, immunized mice have challenged SC in the footpad with L. major parasites. To investigate the rate of protection and the type of immune response generated in mice, lesions development was assessed, IL-4 and IFN-γ levels with the ratio of IgG2a/IgG1 isotype were studied to describe the type of generated immune response. Results: Mice immunized with all liposomal form of SLA showed smaller footpad swelling and lower parasite burden in the spleen and footpad compared to the group of mice received buffer. However, these formulations did not show protection against leishmaniosis because of a generated mixed Th1/Th2 response in mice characterized by high production of IFN-γ and IL4 and a high titer of IgG1 and IgG2a antibody. Conclusion: Immunization with Lip (DOTAP/DOPE/CHO)-SLA+ was not an appropriate strategy to protect mice against leishmaniosis.

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