Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent

Abstract

Meningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent, Neisseria meningitidis, expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. One of the most potent proinflammatory cytokines, interleukin-1β (IL-1β), is activated following caspase-1 activity in the intracellular multiprotein complex called inflammasome. Inflammasomes are activated by a number of microbial factors as well as danger molecules by a two-step mechanism—priming and licensing of inflammasome activation—but there are no data available regarding a role for inflammasome activation in meningococcal disease. The aim of this study was to investigate if N. meningitidis activates the inflammasome and, if so, the role of bacterial LOS in this activation. Cells were subjected to N. meningitidis, both wild-type (FAM20) and its LOS-deficient mutant (lpxA), and priming as well as licensing of inflammasome activation was investigated. The wild-type LOS-expressing parental FAM20 serogroup C N. meningitidis (FAM20) strain significantly enhanced the caspase-1 activity in human neutrophils and monocytes, whereas lpxA was unable to induce caspase-1 activity as well as to induce IL-1β release. While the lpxA mutant induced a priming response, measured as increased expression of NLRP3 and IL1B, the LOS-expressing FAM20 further increased this priming. We conclude that although non-LOS components of N. meningitidis contribute to the priming of the inflammasome activity, LOS per se is to be considered as the central component of N. meningitidis virulence, responsible for both priming and licensing of inflammasome activation.

Dermal exposure to cobalt studiedin vitroin keratinocytes – effects of cobalt exposure on inflammasome activated cytokines, and mRNA response

“…These data show that HaCaT cells react to CoCl 2 exposure by down-regulating the production of CASP1 mRNA and PYCARD mRNA, while still producing NLRP3 mRNA. This same pattern of inflammasome regulation on the transcriptome level has previously been shown in human immune cells (Idosa et al 2019). Moreover, CoCl 2 has been found to increase the mRNA levels of the inflammasome components NPRP3 and IL1B as well as PYCARD/ASC in free fatty acid-primed liver cells (Hern andez et al 2020).…”

Canonical and Non-canonical Inflammasome Activation by Outer Membrane Vesicles Derived From Bordetella pertussis

“…LPS chemical structure can be described into three parts: the most conserved lipid A moiety; a core oligosaccharide chain; and a variable polysaccharide chain known as “O-antigen.” With structural differences respect to other species, B. pertussis has a penta-acylated lipid A lipooligosaccharide that lacks an O-side chain, having in its place a non-repeating trisaccharide ( 51 ). LOS per se from other pathogens are able to be considered as key component responsible for both priming and licensing of inflammasome activation inducing caspase-1 activation ( 52 ). In this context, we decided to determine the contribution of BpLOS present in BpOMVs in inflammasome activation.…”

A meta-analytic evaluation of sex differences in meningococcal disease incidence rates in 10 countries

“…The extensive release of lipooligosaccharide (LOS) from N. meningitidis causes immune cell activation and release of proinflammatory cytokines [51]. The innate immune system expresses pattern recognition receptors (PRRs), which include the Toll-like receptors as the key factor for N. meningitidis LOS detection, evoke an intense inflammatory response [52]. All these factors could potentially be affected by sex hormones and explain, at least in part, the excess meningococcal IR observed in young males.…”