Browsing by Author "Scott, Phillip"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions.
    (2005) Oliveira, Marcia Rosa de; Tafuri, Wagner Luiz; Afonso, Luís Carlos Crocco; Oliveira, Milton Adriano Pelli de; Nicoli, Jacques Robert; Vieira, Etel Rocha; Scott, Phillip; Melo, Maria Norma; Vieira, Leda Quercia
    In order to investigate the importance of the host microbiota on differentiation of T cell subsets in response to infection, Swiss/NIH germ-free mice and conventional (microbiota-bearing) mice were infected with Leishmania major, and lesion development, parasite loads, and cytokine production were assessed. Germ-free mice failed to heal lesions and presented a higher number of parasites at the site of infection than their conventional counterparts. In addition, histopathological analysis indicated a higher density of parasitized macrophages in lesions from germ-free mice than in conventional mice. The initial production of interleukin (IL)-12 and interferon-gamma (IFN-c) in germ-free mice was comparable to the conventional controls. Also, germ-free mice produced elevated levels of IFN-c and lower levels of IL-4 throughout the course of infection, suggesting the development of a Th1 response. Macrophages from germ-free mice exposed to IFN-c and infected with amastigotes in vitro were not as efficient at killing parasites as macrophages from conventional animals. These observations indicate that the microbiota is not essential for the development of Th1 immune responses, but seems to be important for macrophage activation.
  • No Thumbnail Available
    Item
    Infection with Leishmania major induces interleukin-12 production in vivo.
    (1994) Vieira, Leda Quercia; Hondowicz, Brian D.; Afonso, Luís Carlos Crocco; Wysocka, Maria; Trinchieri, Giorgio; Scott, Phillip
    Experimental infections of mice with the protozoan parasite Leishmania major provide an excellent model for defining the conditions required for generation of CD4 ÷ Thl and Th2 cells in vivo. Since interleukin-12 (IL-12) has been implicated in the development of Thl cells, we investigated whether L. major stimulates IL-12 production in vitro or in vivo. Surprisingly, macrophages cultured in vitro failed to produce IL-12 following L. major infection. In contrast, lymph node cells from C3H mice infected for 2 days with L. major produced elevated levels of IL-12. In order to determine if the inability to stimulate IL-12 production was limited to in vitro infections, we infected macrophages in vivo by inoculating L. major into the peritoneal cavity. Peritoneal cells isolated 24 h later exhibited a significant increase in the number of cells producing IL-12. In addition, supernatants harvested from these cells following culture contained elevated levels of IL-12. These data indicate that L. major infection induces increased IL-12 production in mice.
  • No Thumbnail Available
    Item
    Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and Pentostam.
    (1995) Nabors, Gary S.; Afonso, Luís Carlos Crocco; Farrell, Jay P.; Scott, Phillip
    Successful treatment in allergic, autoimmune, and infectious diseases often requires altering the nature of a detrimental immune response mediated by a particular CD4+ T helper (Th) cell subset. While several factors contribute to the development of CD4+ Thi and Th2 cells, the requirements for switching an established response are not understood. Here we use infection with Leishmania major as a model to investigate those requirements. We report that treatment with interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal drug Pentostam, induces healing in L. major-infected mice and that healing is associated with a switch from a Th2 to a Thl response. The data suggest that decreasing antigen levels may be required for IL-12 to inhibit a Th2 response and enhance a Thi response. These observations are important for treatment of nonhealing forms of human leishmaniasis and also demonstrate that in a chronic infectious disease an inappropriate Th2 response can be switched to an effective Thi response.