Characterization of the effects of Interferon gamma protein-10 (CXCL10) against the protozoan parasite Leishmania amazonesis

Show full item record

Title: Characterization of the effects of Interferon gamma protein-10 (CXCL10) against the protozoan parasite Leishmania amazonesis
Author: Rene Ernesto Vasquez
Abstract: Leishmania amazonensis causes progressive disease in most inbred strains of mice . We have previously shown that L . amazonensis -infected C57BL /6 mice have profound impairments in expression of pro -inflammatory cytokines , chemokines and in activation of antigen -specific CD4+ T cells . These impairments are independent of IL -4 . The precise mechanism of pathogenesis associated with L . amazonensis infection remains largely unresolved . Since chemokines are essential mediators of leukocyte recruitment and effector cell function , we hypothesized that these molecules are important for the initiation of early responses locally and the eventual control of the infection . In this study , we found that CXCL10 -treated bone marrow -derived macrophages from both BALB /c and C57BL /6 mice showed decreased numbers of L . amazonensis parasites , which was partially due to increased nitric oxide production , as well as elevated production of pro -inflammatory chemokines . When susceptible C57BL /6 mice were locally injected with CXCL10 following L . amazonensis infection , there was a significant delay in lesion development and reduction in parasite burdens , accompanied by a 7 - and 3 .5 -fold increase in IFN - & #947 ; and IL -12 secretion , respectively , in re -stimulated lymph node cells . This study confirms that CXCL10 assists in the reduction of intracellular parasites . To address the mechanism underlying this enhanced immunity we utilized stationary promastigotes to infect bone marrow -derived DCs of C57BL /6 mice and assessed the activation of DC subsets and the capacity of these DC subsets in priming CD4+ T cells in vitro . We found that CXCL10 induced IL -12p40 , but reduced IL -10 production in DCs . Yet , L . amazonensis -infected DCs produced elevated levels of IL -10 , despite CXCL10 treatment . Elimination of endogenous IL -10 led to increased responsiveness to CXCL10 treatment , as judged by increased IL -12 production in DCs , as well as increased proliferation and IFN - & #947 ; production by CD4+ T cells . In addition , CXCL10 -treated CD4+ T cells became more responsive to IL -12 via increased expression of the IL -12R & #946 ;2 chain and produced elevated IFN - & #947 ; . This study indicates the interplay between CXCL10 and IL -10 in the generation of Th1 -favored , pro -inflammatory responses and further highlights the utility of CXCL10 as a potential therapeutic for the control of non -healing cutaneous leishmaniasis .
URI: http : / /hdl .handle .net /2152 .3 /157
Date: 2007-06-26

Citation

Characterization of the effects of Interferon gamma protein-10 (CXCL10) against the protozoan parasite Leishmania amazonesis. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /157 .

Files in this item

Files Size Format View
REVasquez.pdf 1.115Mb application/pdf View/Open

This item appears in the following Collection(s)

Show full item record

Search DSpace

Advanced Search

Browse