Key Points
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The nuclear factor-κB (NF-κB) family of transcription factors plays a central part in orchestrating the innate and adaptive immune response against invading microbial pathogens. Successful pathogens have acquired multiple mechanisms to control the signalling pathways that regulate the NF-κB cascade, and they can collectively target every aspect of the NF-κB signalling pathway. This Review focuses on the different strategies used by viruses, bacteria and parasites to manipulate NF-κB functions.
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The essential role of NF-κB family members in protection against viruses, bacteria and parasites has been established by the observation that knocking down (ablating) the expression of any of the NF-κB components or blocking their signalling function increases host susceptibility to diverse microbial pathogens.
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Viruses are obligate intracellular parasites and frequently either activate or inhibit the NF-κB signalling pathway during different phases of their life cycle. So, a delicate balance must be maintained between activation and inhibition of the NF-κB pathway. Some viruses uniquely activate NF-κB to promote viral replication and to control virus-induced cellular apoptosis.
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Viruses usually activate or suppress the NF-κB signalling pathway by modulating the function of multiple signalling receptors, adaptor molecules, cellular kinases, and cellular NF-κB inhibitors or regulators, and also by direct interaction with the NF-κB subunits themselves. Virus-encoded proteins can also sometimes modulate the transcriptional activity of activated NF-κB after translocation to the nucleus.
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Bacteria and parasites can activate or inhibit the NF-κB signalling pathway, depending on the host cellular status that most benefits the pathogen. Bacteria-derived molecules can modulate NF-κB by targeting the same pathway components and stages as are targeted by viruses. Sometimes, bacteria and parasites can hijack crucial NF-κB signalling molecules and re-appropriate them for exploitation during the pathogen's own replication cycle.
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Although virus- and bacteria-derived molecules are remarkably diverse in structure, they often target operationally common NF-κB signalling molecules for modulation. Interestingly, a single pathogen often encodes multiple proteins to modulate the NF-κB signalling pathway at different steps, which affirms the key importance of the NF-κB pathway in combating diverse invading microbial pathogens.
Abstract
The nuclear factor-κB (NF-κB) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF-κB proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF-κB signalling pathways by deploying subversive proteins or hijacking the host signalling molecules. Here, we describe the mechanisms by which viruses and bacteria micromanage the host NF-κB signalling circuitry to favour the continued survival of the pathogen.
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Rahman, M., McFadden, G. Modulation of NF-κB signalling by microbial pathogens. Nat Rev Microbiol 9, 291–306 (2011). https://doi.org/10.1038/nrmicro2539
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DOI: https://doi.org/10.1038/nrmicro2539
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