Hydrogen peroxide release by bacteria suppresses inflammasome-dependent innate immunity

Abstract

Hydrogen peroxide (H 2 O 2 ) has a major function in host-microbial interactions. Although most studies have focused on the endogenous H 2 O 2 produced by immune cells to kill microbes, bacteria can also produce H 2 O 2 . How microbial H 2 O 2 influences the dynamics of host-microbial interactions is unclear. Here we show that H 2 O 2 released by Streptococcus pneumoniae inhibits inflammasomes, key components of the innate immune system, contributing to the pathogen colonization of the host. We also show that the oral commensal H 2 O 2 -producing bacteria Streptococcus oralis can block inflammasome activation. This study uncovers an unexpected role of H 2 O 2 in immune suppression and demonstrates how, through this mechanism, bacteria might restrain the immune system to co-exist with the host.

Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome

“…The oxidized mitochondrial DNA binds to NLRP3, promotes NLRP3 inflammasome assembly and activates the NLRP3 inflammasome [25]. Although a low level of ROS promotes NLRP3 inflammasome activation, a recent study demonstrated that a high level of ROS generated by Streptococcus pneumonia infection inhibited the NLRP3 inflammasome through the oxidation of the inflammasome components ASC and caspases [30]. We found that although 4-HAB increased mitochondrial ROS production ( Figure 2B), it significantly reduced mitochondrial integrity loss induced by MSU crystals (Figure 2A).…”

Inflammasome activation and regulation: toward a better understanding of complex mechanisms

“…For example, bacteria such as Streptococcus spp. can restrain inflammasome activation by producing hydrogen peroxide, which in turn dampens bacterial clearance from host cells 28 .…”

The Role of NLRP3 Inflammasome in Pneumococcal Infections

“…Detection of the processed forms of IL-1b and caspase-1 was highly delayed and remained undetectable until 12 h post infection. However, the ratio of processed IL-1b and caspase-1 to their precursors was still very low (100). In contrast, spxB-mutant strain, which lacked H 2 O 2 production, showed an intrinsically increased capacity to activate the inflammasome.…”

“…In contrast to PLY, only one study investigated the pneumococci-derived H 2 O 2 and inflammasome interplay. By utilizing mouse bone marrow-derived macrophages (mBMDMs), Ertmann and Gekara have shown that mBMDMs infected with pneumococci accumulate large amounts of pro-IL-1b and procaspase-1 (100). Detection of the processed forms of IL-1b and caspase-1 was highly delayed and remained undetectable until 12 h post infection.…”