TY - JOUR
T1 - T cell hypo-responsiveness against Leishmania major in MAP kinase phosphatase (MKP) 2 deficient C57BL/6 mice does not alter the healer disease phenotype
AU - Schroeder, Juliane
AU - McGachy, H. Adrienne
AU - Woods, Stuart
AU - Plevin, Robin
AU - Alexander, James
PY - 2013/2/21
Y1 - 2013/2/21
N2 - We have recently demonstrated that MAP kinase phosphatase 2 (MKP-2) deficient C57BL/6 mice, unlike their wild-type counterparts, are unable to control infection with the protozoan parasite Leishmania mexicana. Increased susceptibility was associated with elevated Arginase-1 levels and reduced iNOS activity in macrophages as well as a diminished TH1 response. By contrast, in the present study footpad infection of MKP-2−/− mice with L. major resulted in a healing response as measured by lesion size and parasite numbers similar to infected MKP-2+/+ mice. Analysis of immune responses following infection demonstrated a reduced TH1 response in MKP-2−/− mice with lower parasite specific serum IgG2b levels, a lower frequency of IFN-γ and TNF-α producing CD4+ and CD8+ T cells and lower antigen stimulated spleen cell IFN-γ production than their wild-type counterparts. However, infected MKP-2−/− mice also had similarly reduced levels of antigen induced spleen and lymph node cell IL-4 production compared with MKP-2+/+ mice as well as reduced levels of parasite-specific IgG1 in the serum, indicating a general T cell hypo-responsiveness. Consequently the overall TH1/TH2 balance was unaltered in MKP-2−/− compared with wild-type mice. Although non-stimulated MKP-2−/− macrophages were more permissive to L. major growth than macrophages from MKP-2+/+ mice, reflecting their reduced iNOS and increased Arginase-1 expression, LPS/IFN-γ activation was equally effective at controlling parasite growth in MKP-2−/− and MKP-2+/+ macrophages. Consequently, in the absence of any switch in the TH1/TH2 balance in MKP-2−/− mice, no significant change in disease phenotype was observed.
AB - We have recently demonstrated that MAP kinase phosphatase 2 (MKP-2) deficient C57BL/6 mice, unlike their wild-type counterparts, are unable to control infection with the protozoan parasite Leishmania mexicana. Increased susceptibility was associated with elevated Arginase-1 levels and reduced iNOS activity in macrophages as well as a diminished TH1 response. By contrast, in the present study footpad infection of MKP-2−/− mice with L. major resulted in a healing response as measured by lesion size and parasite numbers similar to infected MKP-2+/+ mice. Analysis of immune responses following infection demonstrated a reduced TH1 response in MKP-2−/− mice with lower parasite specific serum IgG2b levels, a lower frequency of IFN-γ and TNF-α producing CD4+ and CD8+ T cells and lower antigen stimulated spleen cell IFN-γ production than their wild-type counterparts. However, infected MKP-2−/− mice also had similarly reduced levels of antigen induced spleen and lymph node cell IL-4 production compared with MKP-2+/+ mice as well as reduced levels of parasite-specific IgG1 in the serum, indicating a general T cell hypo-responsiveness. Consequently the overall TH1/TH2 balance was unaltered in MKP-2−/− compared with wild-type mice. Although non-stimulated MKP-2−/− macrophages were more permissive to L. major growth than macrophages from MKP-2+/+ mice, reflecting their reduced iNOS and increased Arginase-1 expression, LPS/IFN-γ activation was equally effective at controlling parasite growth in MKP-2−/− and MKP-2+/+ macrophages. Consequently, in the absence of any switch in the TH1/TH2 balance in MKP-2−/− mice, no significant change in disease phenotype was observed.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84874780289&partnerID=MN8TOARS
U2 - 10.1371/journal.pntd.0002064
DO - 10.1371/journal.pntd.0002064
M3 - Article
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
ER -