Modulation of Inflammasome Pathways by Bacterial and Viral Pathogens

Abstract

Inflammasomes are emerging as key regulators of the host response against microbial pathogens. These cytosolic multiprotein complexes recruit and activate the cysteine protease caspase-1 when microbes invade sterile tissues or elicit cellular damage. Inflammasome-activated caspase-1 induces inflammation by cleaving the proinflammatory cytokines IL-1β and IL-18 into their biologically active forms and by releasing the alarmin HMGB1 into the extracellular milieu. Additionally, inflammasomes counter bacterial replication and clear infected immune cells through an inflammatory cell death program termed pyroptosis. As a countermeasure, bacterial and viral pathogens evolved virulence factors to antagonize inflammasome pathways. In this review, we discuss recent progress on how inflammasomes contribute to host defense against bacterial and viral pathogens, and we review how viruses and bacteria modulate inflammasome function to their benefit.

Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation

“…It therefore is tempting to speculate that the high frequency of heterozygous MEFV mutations in endemic FMF regions (42) might be related to their rendering Pyrin activation insensitive to microtubule manipulations by such pathogens. Given the key role of inflammasomes in antimicrobial host defense (43), the ability to engage the Pyrin inflammasome in the presence of microtubule dynamics blockade is likely to have offered heterozygous individuals a selective advantage in clearing such infections. Finally, the insight that inflammasome activation by FMF Pyrin resists colchicine blockade enables functional/immunological screening of the disease among clinically overlapping autoinflammatory patients and thus may contribute to timely diagnosis and commencement of therapy in the future.…”

Tributes, conferences and listening to authors

“…For example, research in EJI by Ari Waisman and colleagues was the first to prove the plasticity of Th17 [8], a finding confirmed and extended by others in 2011 [9]. We are also publishing on fast moving fields, as evidenced by recent reviews [10][11][12][13], such as innate lymphoid cells [14], gut homeostasis [15] and innate immunity [16] to name but a few, as well as established fields such as B cells [17], NK cells [18] and macrophages -the latter being the subject of an excellent Viewpoint series led by Siamon Gordon and Alberto Mantovani [19]. By doing so, EJI continues to fulfill its remit as a broad immunology journal that not only publishes that which is currently considered ''sexy''.…”

Burn the house, save the day: pyroptosis in pathogen restriction

“…Brought to you by | University of Queensland -UQ Library Authenticated Download Date | 4/9/15 1:05 AM activation and the production of protease inhibitors to prevent inflammatory caspase activity, and are discussed in greater detail elsewhere [39].…”