T cell cytokine receptor (TCCR)/WSX-1 is required for efficient development of Th1 response in cutaneous leishmaniasis caused by Leishmania mexicana
MetadataShow full item record
Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Microbiology Honors Theses; 2007
The Ohio State University. Department of Sociology Honors Theses; 2007
Lesion development and Leishmania mexciana specific immune responses were measured in T cell cytokine receptor knockout (TCCR -/-) mice and compared to similarly infected wildtype (TCCR +/+) control mice. In comparison to TCCR +/+ mice, TCCR -/- mice developed larger ulcerating lesions containing higher parasite loads following inoculation with 1000 L. mexicana amastigotes into ear dermis. These differences became significant nine weeks after infection. Previous studies have found that the interleukin 27 (IL-27)/TCCR signaling pathway mediates susceptibility to visceral leishmaniasis caused by Leishmania donovani, but plays a minor role in determining outcome of cutaneous leishmaniasis resulting from Leishmania. major infection. However the results of the present study provide new observations related to IL-27 signaling and cutaneous leishmaniasis caused by L. mexicana. Specific immunologic responses of L. mexicana infected TCCR -/- and TCCR +/+ mice were therefore examined both in vivo and in vitro. In comparison to TCCR +/+ infected with L. mexicana, TCCR -/- mice generated minimal levels of type 1 (Th1)-associated immunoglobulin G2a (IgG2a) antibodies. Additionally TCCR -/- mice up-regulated parasite specific immunoglobulin G1 (IgG1) antibodies as infection progressed indicating a dominant type-2 (Th2) response in TCCR -/- mice. Furthermore, draining lymph node cells and splenocytes harvested from L. mexicana infected TCCR -/- mice and stimulated in vitro with L. mexicana (Lm-Ag) antigen produced substantially less IFN-γ, but more Il-4 and Il-10 as compared to TCCR +/+ counterparts. This again indicates a predominately Th2-influenced immune response rather than Th1 response in TCCR -/- mice infected with L. mexicana. These results demonstrate that whereas the IL-27/TCCR signaling pathway is dispensable against infection with L. major, it is required to mount a Th1 response and control cutaneous leishmaniasis caused by L. mexicana.
Denman Undergraduate Research Forum, 4th place
A one-year embargo was granted for this item.
Items in Knowledge Bank are protected by copyright, with all rights reserved, unless otherwise indicated.