IL-13 gene-deficient mice are susceptible to cutaneous L. mexicana infection.
Recent studies have demonstrated that IL-13 mediates susceptibility to cutaneous L. major infection via IL-4-independent pathway. To determine whether IL-13 also plays a similar role in pathogenesis of cutaneous L. mexicana infection, we analyzed the course of L. mexicana infection in IL-13(-/-) and IL-4/IL-13(-/-) C57BL/6x129sv/Ev mice and compared with that in similarly infected wild-type mice. IL-13(-/-) mice were as susceptible as the wild-type mice to L. mexicana and developed rapidly progressing, large non-healing lesions following cutaneous L. mexicana infection. In contrast, similarly infected IL-4/IL-13(-/-) mice were highly resistant and developed either no lesions or small lesions containing few parasites that totally resolved by 12 weeks following infection. Throughout the course of infection IL-13(-/-) and the wild-type mice produced significantly more Th2-associated L. mexicana antigen (LmAg)-specific IgG1 than IL-4/IL-13(-/-) mice. All three groups produced comparable levels of Th1-associated IgG2a. At week 12 post infection, LmAg-stimulated spleen cells from L. mexicana-infected IL-4/IL-13(-/-) produced significantly higher levels of IL-12 and IFN-gamma as compared to those from similarly infected wild-type and IL-13(-/-) mice. Although both IL-13(-/-) and the wild-type spleen cells produced IL-4 following in vitro antigenic stimulation, the wild-type mice produced significantly more. These findings demonstrate that IL-13 is not involved in mediating susceptibility to L. mexicana. Moreover, they also indicate that IL-4 not IL-13 is a dominant cytokine involved in pathogenesis of cutaneous L. mexicana infection.
Sosa
M R
MR
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, USA.
Rosas
L E
LE
McKenzie
A N
AN
Satoskar
A R
AR
D000818:Animals; D004198:Disease Susceptibility; D018793:Interleukin-13 / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D007894:Leishmania mexicana; D016773:Leishmaniasis, Cutaneous / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D018793:Interleukin-13; D015847:Interleukin-4