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Critical role of type I interferon-induced macrophage necroptosis during infection with Salmonella enterica serovar Typhimurium

Cellular & Molecular Immunology volume 10, pages 99–100 (2013)Cite this article

Salmonella enteric strains are facultative intracellular pathogens that can produce both localized enteritis and disseminated systemic disease in humans and a variety of other vertebrates.1 Extensive evidence obtained from genetic and cell biology studies indicates that Salmonella has evolved specific virulence mechanisms to evade innate immune responses.1 However, the underlying molecular and cellular mechanisms have not been understood very well. A recent paper published by Robinson et al. in Nature Immunology2 reported that type I interferon (IFN)-induced macrophage necroptosis plays a critical role in evading host innate immune responses during infection with Salmonella enterica serovar Typhimurium (S. Typhimurium). This finding helps us to further understand the pathogenesis of Salmonella enteric infection.

The macrophage, an important component of innate immune cells, has long been thought to be central to the dissemination of S. Typhimurium.3 Macrophages are among the earliest activated lymphocytes controlling the infectious pathogens before adaptive immune responses are developed. Macrophages provide an effective mechanism in rapid control of intracellular bacteria such as S. Typhimurium in the early phase of infection.4,5 During the host bacteria interaction, virulent S. Typhimurium develops several mechanisms to avoid killing by host's macrophages.6 The bacterium controls maturation of the intracellular vacuole where it shields itself from cytosol macrophage degradative pathway. In addition, S. Typhimurium has the ability to avoid killing by free radical-dependent macrophage antimicrobial mechanisms.6 Further, the intracellular bacteria such as S. Typhimurium induce the macrophage death, which is a key virulence strategy used by those bacterial to evading host innate immune responses.5 However, the underlying mechanism has not been elucidated very well. Regarding the processes of the pathogen-induced macrophage death including the well-known apoptosis and necrosis, the cells can also die through the inflammasome-mediated pyrosis, which involves in inflammatory process of caspase-1-dependent programmed cell death and proinflammatory cytokine release during cell lysis. Recently, a novel ‘prototypic’ apoptotic pathway termed as necropotosis has been defined. The necropotosis is normally triggered by Fas and TNFR family of death receptors and this programmed cell necrosis is competitive with apoptosis.7,8 The necroptosis pathway depends on formation of death domain-containing kinase RIP1 and RIP3 complex and subsequent recruitment of downstream adaptor proteins, such as Fas-associated death domain protein, and upstream caspases, such as caspase-8.7,8 The new findings reported by Robinson et al.2 has demonstrated that S. Typhimurium exploites type I IFN to induce necroptosis of macrophages. This sheds light on the importance of S. Typhimurium-induced macrophage necroptosis in the pathogenesis of the infection.

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  1. Key lab for immunology in Universities of Shandong province, Weifang Medical University, Weifang, 261053, China

    Shujuan Liang

  2. Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA

    Xuebin Qin

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  1. Shujuan Liang
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Correspondence to Xuebin Qin.

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Liang, S., Qin, X. Critical role of type I interferon-induced macrophage necroptosis during infection with Salmonella enterica serovar Typhimurium. Cell Mol Immunol 10, 99–100 (2013). https://doi.org/10.1038/cmi.2012.68

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