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Impairment of STATActivation by IL-12in a Patient withAtypicalMycobacterial andStaphylococcalInfections Jared GollobKorina G. VeenstraHarumi Jyonouchi2000 год

Impairment of STAT Activation by IL-12 in a Patient with Atypical Mycobacterial and Staphylococcal Infections
статья из журнала

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Аннотация: Abstract IL-12 plays a pivotal role in the stimulation of immune responses against intracellular infections. This role is manifested in the increased susceptibility to atypical mycobacterial and salmonella infections among individuals whose lymphocytes lack expression of IL-12Rβ1. Here, we report on a patient with Mycobacterium avium infection, recurrent Staphylococcus aureus sinusitis, and multiple adverse drug reactions whose T cells were unable to produce IFN-γ or proliferate in response to IL-12 despite the expression of wild-type IL-12Rβ1 and IL-12Rβ2. The defect in these functional responses to IL-12 was selective, as cytolytic activity induced by IL-12 was intact, and lymphocytes were responsive to stimulation by IL-2. An examination of cytokine signaling revealed that STAT4 and extracellular regulated kinase 1 (ERK1) activation by IL-12 was intact, whereas the activation of STAT1, -3, and -5 by IL-12 was lost. This impairment of STAT activation was specific for IL-12, as STAT activation by IL-2, IL-15, and IFN-γ was unaffected. These findings demonstrate that the activation of STAT4 alone is not sufficient for IL-12-induced IFN-γ production and proliferation and suggest that other STATs play a role in these responses to IL-12. While the etiology of the impaired IL-12 signaling in this patient has not yet been elucidated, the absence of mutations in IL-12Rβ1 or IL-12Rβ2 and the preservation of STAT4 activation raise the possibility that there may be a mutation in an as yet undiscovered component of the IL-12 signaling complex that is normally required for the recruitment and activation of STAT1, -3, and -5.
Год издания: 2000
Авторы: Jared Gollob, Korina G. Veenstra, Harumi Jyonouchi, Anne M. Kelly, Patricia Ferrieri, David J. Panka, Frédéric Altare, Claire Fieschi, Jean‐Laurent Casanova, David A. Frank, James W. Mier
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: Cytokine Signaling Pathways and Interactions, Mycobacterium research and diagnosis, Medicinal Plant Pharmacodynamics Research
Другие ссылки: The Journal of Immunology (HTML)
PubMed (HTML)