T Cell Hypo-Responsiveness against Leishmania major in MAP Kinase Phosphatase (MKP) 2 Deficient C57BL/6 Mice Does Not Alter the Healer Disease Phenotype

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. © 2013 schroeder et al.