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Mosser, Elise M.; Rest, Richard F.

doi:10.1186/1471-2180-6-56

Cited by 51 publications

(23 citation statements)

References 42 publications

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“…These cells may have susceptibility to cholesterol-dependent cytolysins different from macrophages (43). Regardless, the reason for their eventual clearance remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion

et al. 2016

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dStreptococcus pneumoniae (the pneumococcus) is capable of invading the heart. Herein we observed that pneumococcal invasion of the myocardium occurred soon after development of bacteremia and was continuous thereafter. Using immunofluorescence microscopy (IFM), we observed that S. pneumoniae replication within the heart preceded visual signs of tissue damage in cardiac tissue sections stained with hematoxylin and eosin. Different S. pneumoniae strains caused distinct cardiac pathologies: strain TIGR4, a serotype 4 isolate, caused discrete pneumococcus-filled microscopic lesions (microlesions), whereas strain D39, a serotype 2 isolate, was, in most instances, detectable only using IFM and was associated with foci of cardiomyocyte hydropic degeneration and immune cell infiltration. Both strains efficiently invaded the myocardium, but cardiac damage was entirely dependent on the pore-forming toxin pneumolysin only for D39. Early microlesions caused by TIGR4 and microlesions formed by a TIGR4 pneumolysin-deficient mutant were infiltrated with CD11b؉ and Ly6G-positive neutrophils and CD11b ؉ and F4/80-positive (F4/80 ؉ ) macrophages. We subsequently demonstrated that macrophages in TIGR4-infected hearts died as a result of pneumolysin-induced necroptosis. The effector of necroptosis, phosphorylated mixed-lineage kinase domain-like protein (MLKL), was detected in CD11b؉ and F4/80 ؉ cells associated with microlesions. Likewise, treatment of infected mice and THP-1 macrophages in vitro with the receptor-interacting protein 1 kinase (RIP1) inhibitor necrostatin-5 promoted the formation of purulent microlesions and blocked cell death, respectively. We conclude that pneumococci that have invaded the myocardium are an important cause of cardiac damage, pneumolysin contributes to cardiac damage in a bacterial strain-specific manner, and pneumolysin kills infiltrated macrophages via necroptosis, which alters the immune response.

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“…These cells may have susceptibility to cholesterol-dependent cytolysins different from macrophages (43). Regardless, the reason for their eventual clearance remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion

et al. 2016

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“…In the anthrax-producing bacterium Bacillus anthracis , the components of anthrax toxin (lethal factor (LF), oedema factor (EF; also known as Cya) and protective antigen (PA)), as well as the cholesterol-dependent cytolysin anthrolysin (ALO), are found in the EV pellet of the bacterial cell culture after centrifugation, but not in the supernatant, suggesting that the overwhelming majority of toxin released from cells is encapsulated in EVs 4,84,85 (FIG. 3a).…”

Section: Cargo and Functions Of Extracellular Vesiclesmentioning

confidence: 99%

Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi

Wolf²,

et al. 2015

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Extracellular vesicles (EVs) are produced by all domains of life. In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs escape the thick cell walls of Gram-positive bacteria, mycobacteria and fungi is still unknown. Nonetheless, EVs have been described in a variety of cell-walled organisms, including Staphylococcus aureus, Mycobacterium tuberculosis and Cryptococcus neoformans. These EVs contain varied cargo, including nucleic acids, toxins, lipoproteins and enzymes, and have important roles in microbial physiology and pathogenesis. In this Review, we describe the current status of vesiculogenesis research in thick-walled microorganisms and discuss the cargo and functions associated with EVs in these species.

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“…The cholesterol-dependent cytolysins (CDCs) are the major virulence factors associated with the disease pathogenesis of Listeria monocytogenes (listeriolysin) (55), Streptococcus pyogenes (streptolysin) (72), Streptococcus pneumoniae (pneumolysin) (56)(57)(58), and Bacillus anthracis (anthrolysin) (59). It has been proposed that bacterial CDCs can cause an increased production of proinflammatory cytokines through a TLR4-mediated response (60,61).…”

Section: Fig 9 Proinflammatory Mediator Expression In Tlr4mentioning

confidence: 99%

Unexpected Roles for Toll-Like Receptor 4 and TRIF in Intraocular Infection with Gram-Positive Bacteria

et al. 2015

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Inflammation caused by infection with Gram-positive bacteria is typically initiated by interactions with Toll-like receptor 2 (TLR2). Endophthalmitis, an infection and inflammation of the posterior segment of the eye, can lead to vision loss when initiated by a virulent microbial pathogen. Endophthalmitis caused by Bacillus cereus develops as acute inflammation with infiltrating neutrophils, and vision loss is potentially catastrophic. Residual inflammation observed during B. cereus endophthalmitis in TLR2 ؊/؊ mice led us to investigate additional innate pathways that may trigger intraocular inflammation. We first hypothesized that intraocular inflammation during B. cereus endophthalmitis would be controlled by MyD88-and TRIF-mediated signaling, since MyD88 and TRIF are the major adaptor molecules for all bacterial TLRs. In MyD88 ؊/؊ and TRIF ؊/؊ mice, we observed significantly less intraocular inflammation than in eyes from infected C57BL/6J mice, suggesting an important role for these TLR adaptors in B. cereus endophthalmitis. These results led to a second hypothesis, that TLR4, the only TLR that signals through both MyD88 and TRIF signaling pathways, contributed to inflammation during B. cereus endophthalmitis. Surprisingly, B. cereus-infected TLR4 ؊/؊ eyes also had significantly less intraocular inflammation than infected C57BL/6J eyes, indicating an important role for TLR4 in B. cereus endophthalmitis. Taken together, our results suggest that TLR4, TRIF, and MyD88 are important components of the intraocular inflammatory response observed in experimental B. cereus endophthalmitis, identifying a novel innate immune interaction for B. cereus and for this disease. Bacillus cereus is a Gram-positive, spore-forming, and beta-hemolytic soil bacterium (1). Commonly identified as a causative agent of foodborne illnesses, B. cereus is also associated with a multitude of clinical conditions, such as central nervous system infections (2), pneumonia (3), endocarditis (4), and gas-gangrene-like cutaneous infections (5). B. cereus also causes a virulent form of endophthalmitis, an intraocular inflammatory condition resulting from the introduction of microorganisms into the posterior segment of the eye following surgery or injury or from a distant site of infection. This infection causes irreversible damage to the retina, often leading to vision loss within 1 or 2 days (6). Typically, B. cereus endophthalmitis occurs following a penetrating eye injury (posttraumatic) with retained intraocular foreign bodies (7, 8) but has also been reported in postoperative patients (9-11). Fewer than 30% of posttraumatic B. cereus endophthalmitis patients retained useful vision, and out of these, only 9% retained 20/70 vision or better (7, 12). Moreover, 48% of B. cereus and other Bacillus species infections required evisceration or enucleation of the eye despite therapeutic intervention (7, 12). Intraocular inflammation that occurs during B. cereus endophthalmitis interferes with the clarity of the visual axis, contributing to disruption...

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Untitled

Cited by 51 publications

References 42 publications

Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion

Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion

Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi

Unexpected Roles for Toll-Like Receptor 4 and TRIF in Intraocular Infection with Gram-Positive Bacteria

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