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Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with mycobacterium tuberculosis.

Cooper AM, Magram J, Ferrante J, Orme IM - J. Exp. Med. (1997)

Bottom Line: Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation.The cytokine-mediating macrophage activation is interferon-gamma (IFN-gamma), which is largely dependent on interleukin-12 (IL-12) for its induction.T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40(-/-) mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA.

ABSTRACT
Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation. The cytokine-mediating macrophage activation is interferon-gamma (IFN-gamma), which is largely dependent on interleukin-12 (IL-12) for its induction. To address the role of IL-12 in immunity to tuberculosis, IL-12 p40(-/-) mice were infected with M. tuberculosis and their capacity to control bacterial growth and other characteristics of their immune response were determined. The IL-12 p40(-/-) mice were unable to control bacterial growth and this appeared to be linked to the absence of both innate and acquired sources of IFN-gamma. T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40(-/-) mice. Therefore, IL-12 is essential to the generation of a protective immune response to M. tuberculosis, with its main functions being the induction of the expression of IFN-gamma and the activation of antigen-specific lymphocytes capable of creating a protective granuloma.

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Related in: MedlinePlus

IL-12 p40−/− mice  cannot make IFN-γ protein in  response to M. tuberculosis infection. Splenocytes from naive (a)  or infected (b) mice were cultured, in vitro, at a concentration  of 2 × 105 cells per well in 96-well plates. In a, the cells from  naive control (solid bars) or IL-12  p40−/− (striped bars) mice were  exposed to live bacilli in the  presence or absence of anti-cytokine antibodies (ND, not determined). In b, the cells from infected control (solid circles) or IL-12  p40−/− (open circles) mice were  exposed to purified culture filtrate proteins derived from M.  tuberculosis. The cells were cultured for 4 d and the supernatants were then analyzed by  sandwich ELISA for IFN-γ.
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Figure 3: IL-12 p40−/− mice cannot make IFN-γ protein in response to M. tuberculosis infection. Splenocytes from naive (a) or infected (b) mice were cultured, in vitro, at a concentration of 2 × 105 cells per well in 96-well plates. In a, the cells from naive control (solid bars) or IL-12 p40−/− (striped bars) mice were exposed to live bacilli in the presence or absence of anti-cytokine antibodies (ND, not determined). In b, the cells from infected control (solid circles) or IL-12 p40−/− (open circles) mice were exposed to purified culture filtrate proteins derived from M. tuberculosis. The cells were cultured for 4 d and the supernatants were then analyzed by sandwich ELISA for IFN-γ.

Mentions: The role of IFN-γ in initiating a protective Th1 response is well documented and the requirement for this molecule in early T cell activation is established. To determine the levels of IFN-γ protein available in the initial stages of infection the ability of naive splenocytes to release IFN-γ in response to live M. tuberculosis was analyzed. IL-12 p40−/− splenocytes had a much reduced ability to secrete IFN-γ compared with the C57BL/6 splenocytes (Fig. 3 a). The addition of neutralizing antibodies to TNF-α and IL-12 demonstrates the role of both these molecules in driving this response in the C57BL/6 mice (Fig. 3 a).


Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with mycobacterium tuberculosis.

Cooper AM, Magram J, Ferrante J, Orme IM - J. Exp. Med. (1997)

IL-12 p40−/− mice  cannot make IFN-γ protein in  response to M. tuberculosis infection. Splenocytes from naive (a)  or infected (b) mice were cultured, in vitro, at a concentration  of 2 × 105 cells per well in 96-well plates. In a, the cells from  naive control (solid bars) or IL-12  p40−/− (striped bars) mice were  exposed to live bacilli in the  presence or absence of anti-cytokine antibodies (ND, not determined). In b, the cells from infected control (solid circles) or IL-12  p40−/− (open circles) mice were  exposed to purified culture filtrate proteins derived from M.  tuberculosis. The cells were cultured for 4 d and the supernatants were then analyzed by  sandwich ELISA for IFN-γ.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198958&req=5

Figure 3: IL-12 p40−/− mice cannot make IFN-γ protein in response to M. tuberculosis infection. Splenocytes from naive (a) or infected (b) mice were cultured, in vitro, at a concentration of 2 × 105 cells per well in 96-well plates. In a, the cells from naive control (solid bars) or IL-12 p40−/− (striped bars) mice were exposed to live bacilli in the presence or absence of anti-cytokine antibodies (ND, not determined). In b, the cells from infected control (solid circles) or IL-12 p40−/− (open circles) mice were exposed to purified culture filtrate proteins derived from M. tuberculosis. The cells were cultured for 4 d and the supernatants were then analyzed by sandwich ELISA for IFN-γ.
Mentions: The role of IFN-γ in initiating a protective Th1 response is well documented and the requirement for this molecule in early T cell activation is established. To determine the levels of IFN-γ protein available in the initial stages of infection the ability of naive splenocytes to release IFN-γ in response to live M. tuberculosis was analyzed. IL-12 p40−/− splenocytes had a much reduced ability to secrete IFN-γ compared with the C57BL/6 splenocytes (Fig. 3 a). The addition of neutralizing antibodies to TNF-α and IL-12 demonstrates the role of both these molecules in driving this response in the C57BL/6 mice (Fig. 3 a).

Bottom Line: Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation.The cytokine-mediating macrophage activation is interferon-gamma (IFN-gamma), which is largely dependent on interleukin-12 (IL-12) for its induction.T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40(-/-) mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA.

ABSTRACT
Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation. The cytokine-mediating macrophage activation is interferon-gamma (IFN-gamma), which is largely dependent on interleukin-12 (IL-12) for its induction. To address the role of IL-12 in immunity to tuberculosis, IL-12 p40(-/-) mice were infected with M. tuberculosis and their capacity to control bacterial growth and other characteristics of their immune response were determined. The IL-12 p40(-/-) mice were unable to control bacterial growth and this appeared to be linked to the absence of both innate and acquired sources of IFN-gamma. T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40(-/-) mice. Therefore, IL-12 is essential to the generation of a protective immune response to M. tuberculosis, with its main functions being the induction of the expression of IFN-gamma and the activation of antigen-specific lymphocytes capable of creating a protective granuloma.

Show MeSH
Related in: MedlinePlus