Abstract
The airway epithelium and underlying innate immune cells comprise the first line of host defense in the lung. They recognize pathogen-associated molecular patterns (PAMPs) using membrane-bound receptors, as well as cytosolic receptors such as inflammasomes. Inflammasomes activate inflammatory caspases, which in turn process and release the inflammatory cytokines IL-1β and IL-18. Additionally, inflammasomes trigger a form of lytic cell death termed pyroptosis. One of the most important inflammasomes at the host-pathogen interface is the non-canonical caspase-11 inflammasome that responds to LPS in the cytosol. Caspase-11 is important in defense against Gram-negative pathogens, and can drive inflammatory diseases such as LPS-induced sepsis. However, pathogens can employ evasive strategies to minimize or evade host caspase-11 detection. In this review, we present a comprehensive overview of the function of the non-canonical caspase-11 inflammasome in sensing of cytosolic LPS, and its mechanism of action with particular emphasis in the role of caspase-11 in the lung. We also explore some of the strategies pathogens use to evade caspase-11.
Highlights
Bacterial infections of the respiratory tract remain a leading cause of global morbidity and mortality [1]
guanylate binding proteins (GBPs) can serve as a docking platform to recruit another interferoninducible protein, IRGB10 that can co-localize to the intracellular bacteria to disrupt the bacterial cell membrane and to liberate bacterial ligands, including LPS and DNA, for innate immune recognition [80]
We showed that the NOD-like receptor 4 (NLRC4) inflammasome detects B. thailandensis, and activates caspase-1 to trigger pyroptosis and IL-18 secretion
Summary
Bacterial infections of the respiratory tract remain a leading cause of global morbidity and mortality [1]. Intracellular sensors like inflammasomes are expressed in innate immune cells, lung epithelium, and endothelium to enable detection of pathogens and subsequent protective responses [6,7,8]. Several studies showed that LPS cytosolic access can be mediated by the activity of host factors, such as guanylate binding proteins (GBPs) [61, 62].
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