Your browser doesn't support javascript.
loading
Impaired macrophage responses may contribute to exacerbation of blood-stage Plasmodium chabaudi chabaudi malaria in interleukin-12-deficient mice.
Bastos, Karina R B; Barboza, Renato; Elias, Rosa M; Sardinha, Luiz R; Grisotto, Marcos G; Marinho, Cláudio R F; Amarante-Mendes, Gustavo P; Alvarez, José M; Lima, Maria Regina D'Império.
Afiliação
  • Bastos KR; Departamento de Imunologia, Instituto de Ciências Biomédicas, Av. Prof Lineu Prestes 1730, Universidade de São Paulo, São Paulo, SP Brazil CEP-05508-900.
J Interferon Cytokine Res ; 22(12): 1191-9, 2002 Dec.
Article em En | MEDLINE | ID: mdl-12581492
Aiming to clarify the role of endogenous interleukin-12 (IL-12) in protective immunity against blood stages of Plasmodium chabaudi chabaudi (AS), we evaluated the course of infection in IL-12p40 gene knockout (IL-12p40KO) and wild-type (WT) C57BL/6 mice, focusing (1) on the ability of T cells to develop adequate type 1 responses and (2) on the potentiality of macrophages to respond to parasites, interferon-gamma (IFN-gamma), or both. We observed that IL-12p40KO mice develop significantly higher parasitemias during the acute infection, although mice from both groups clear the parasites within a month and similarly eliminate a secondary challenge. Thus, fully protective immunity to P. c. chabaudi can be generated in the absence of IL-12. However, this cytokine may promote parasite control during the early phase of infection. The increased acute parasitemia of IL-12p40KO mice was associated with both impaired IFN-gamma and nitric oxide (NO) response by spleen cells. Because stimulation with recombinant IFN-gamma (rIFN-gamma) failed to improve the NO response in IL-12p40KO macrophages, we investigated whether these cells have an intrinsic defect. Analysis of peritoneal macrophages revealed that IL-12p40KO cells produce higher levels of transforming growth factor-beta1 (TGF-beta1) compared with WT cells and respond to infected erythrocytes or rIFN-gamma by releasing little NO. Moreover, IL-12p40KO macrophages had a severely impaired ability to internalize opsonized infected erythrocytes, suggesting that the low effector profile assumed by these cells may compromise antibody-mediated immunity. Taken together, our results support the idea that the absence of IL-12p40 not only affects IFN-gamma production but also has deep consequences in macrophage effector functions that may contribute to exacerbation of the early phase of P. c. chabaudi malaria.
Assuntos
Buscar no Google
Base de dados: MEDLINE Assunto principal: Parasitemia / Interleucina-12 / Macrófagos / Malária Limite: Animals Idioma: En Ano de publicação: 2002 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Parasitemia / Interleucina-12 / Macrófagos / Malária Limite: Animals Idioma: En Ano de publicação: 2002 Tipo de documento: Article