An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection.
A comparison of the growth of Leishmania mexicana in IL-4(-/-), IL-4Ralpha(-/-) and wild-type BALB/c mice demonstrated a disease exacerbative role for IL-13 as well as IL-4. Thus, while both IL-4(-/-) and IL-4Ralpha(-/-) mice were more resistant than wild-type controls to infection with L. mexicana, IL-4Ralpha(-/-) mice, which are unresponsive to IL-13 as well as IL-4, were significantly more resistant to parasite growth than their IL-4(-/-) counterparts. Cytokine and antibody analysis revealed a Th1-biased specific response in both infected IL-4(-/-) and IL-4Ralpha(-/-) mice compared with wild-type animals. Reconstituting SCID mice with IL-4(-/-), IL-4Ralpha(-/-) or wild-type splenocytes prior to infection demonstrated that the early onset of lesion growth was dependent on the presence of lymphocytes responding to IL-4 and/or IL-13, as lesions failed to develop in only the SCID IL-4Ralpha(-/-) reconstituted mice. An independent role for IL-13 in L. mexicana infection was demonstrated by comparing disease progression in IL-13(-/-), IL-4(-/-)/IL-13(-/-) and wild-type B6/129 mice. In contrast to IL-4(-/-)/IL-13(-/-) mice, which were resistant, IL-13(-/-) mice developed lesions similar in size to wild-type animals up to week 8 post-infection. However, in contrast to wild-type mice in which disease continued to progress, lesions eventually healed in IL-13(-/-) mice, in association with the development of a Th1 response. Collectively our results suggest that IL-4 plays a critical role in early lesion development, and that IL-13 plays a crucial part in maintaining a chronic non-healing infection.
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D007894:Leishmania mexicana / Q000254:growth & development* / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D019948:Receptors, Interleukin-4 / Q000502:physiology
D000913:Antibodies, Protozoan; D016207:Cytokines; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4