EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Cathepsin L is crucial for a Th1-type immune response during Leishmania major infection



Cathepsin L is crucial for a Th1-type immune response during Leishmania major infection



Microbes and Infection 6(5): 468-474



Prior to the activation of CD4+ T cells, exogenous proteins are digested by endo/lysosomal enzymes in antigen-presenting cells (APCs) to produce antigenic peptides that are presented on major histocompatibility complex class II molecules. In the studies described here, the functional significance of cathepsin L for antigen processing and Th1/Th2 differentiation in experimental leishmaniasis was investigated. We first demonstrated that cathepsin L is one of the candidates for endo/lysosomal enzymes in the processing of soluble Leishmania antigen (SLA) by using CLIK148, a specific inhibitor of cathepsin L. Treatment of BALB/c or DBA/2 mice with CLIK148 exacerbated the disease by enhancing an SLA-specific Th2-type response such as interleukin (IL)-4 production. CLIK148 did not exert any direct influence on Leishmania major promastigotes themselves or on the course of L. major infection in SCID mice. Taken together, these findings suggest that treatment of host mice with CLIK148 affects the processing of SLA in APCs, resulting in the potentiation of Th2-type immune responses and thus leading to exacerbation of the disease. Furthermore, endo/lysosomal cathepsin L was found to be functionally distinct from previously described cathepsins B and D.

(PDF emailed within 0-6 h: $19.90)

Accession: 004065652

Download citation: RISBibTeXText

PMID: 15109961

DOI: 10.1016/j.micinf.2004.01.008



Related references

Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection. Plos Neglected Tropical Diseases 8(9): E3194-E3194, 2016

Treatment with cathepsin L inhibitor potentiates Th2-type immune response in Leishmania major-infected BALB/c mice. International Immunology 13(8): 975-982, 2001

Vaccination with recombinant Parasite Surface Antigen 2 from Leishmania major induces a Th1 type of immune response but does not protect against infection. Vaccine 16(20): 2077-2084, 1998

Vervet monkeys vaccinated with killed Leishmania major parasites and interleukin-12 develop a type 1 immune response but are not protected against challenge infection. Infection and Immunity 69(1): 245-251, 2000

Leishmania major infection in major histocompatibility complex class II-deficient mice: CD8+ T cells do not mediate a protective immune response. Immunobiology 195(2): 243-260, 1996

c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection. European Journal of Immunology 41(5): 1388-1398, 2011

Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response. Plos Neglected Tropical Diseases 6(7): E1741-E1741, 2012

Leishmania major: secreted antigens of Leishmania major promastigotes shift the immune response of the C57BL/6 mice toward Th2 in vitro. Experimental Parasitology 127(1): 46-51, 2011

KM+ lectin induces TH1 immune response and resistance to Leishmania major infection. Glycobiology 11(10): 892, October, 2001

Splenectomy does not interfere with immune response to Leishmania major infection in mice. Cellular Immunology 249(1): 1-7, 2007

The role of the innate immune response in Th1 cell development following Leishmania major infection. Journal of Leukocyte Biology 57(4): 515-522, 1995

An in vitro model for infection with Leishmania major that mimics the immune response in mice. Infection and Immunity 65(7): 2837-2845, 1997

Expression and contribution of B7-1 (CD80) and B7-2 (CD86) in the early immune response to Leishmania major infection. Journal of Immunology 162(11): 6708-6715, 1999

Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection. Journal of Proteome Research 14(1): 318-329, 2015

Experimental Leishmania major infection suppresses HIV-1 DNA vaccine induced cellular immune response. Cells, Tissues, Organs 177(3): 185-188, 2004