T cell hypo-responsiveness against Leishmania major in MAP kinase phosphatase (MKP) 2 deficient C57BL/6 mice does not alter the healer disease phenotype.

• Autores principales: Juliane Schroeder (Autor), H Adrienne McGachy (Autor), Stuart Woods (Autor), Robin Plevin (Autor), James Alexander (Autor)
• Formato: Libro
• Publicado: Public Library of Science (PLoS), 2013-01-01T00:00:00Z.
• Materias: article
• Acceso en línea: Connect to this object online.
• Notes: 1935-2727; 1935-2735; 10.1371/journal.pntd.0002064
• Keywords: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270
• Source: PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2064 (2013)

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 T(H)1 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 T(H)1 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 T(H)1/T(H)2 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 T(H)1/T(H)2 balance in MKP-2(-/-) mice, no significant change in disease phenotype was observed.