Cutaneous Na+ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense

Jantsch, Jonathan; Schatz, Valentin; Friedrich, Diana; Schröder, Agnes; Kopp, Christoph W.; Siegert, Isabel; Maronna, Andreas; Wendelborn, D F; Linz, Peter; Binger, Katrina J.; Gebhardt, M.; Heinig, Matthias; Neubert, Patrick; Fischer, Fabian; Teufel, Stefan; David, Jean‐Pierre; Neufert, Clemens; Cavallaro, Alexander; Rakova, Natalia; Küper, Christoph; Beck, Franz‐Xaver; Neuhofer, Wolfgang; Müller, Dominik N.; Schuler, Gerold; Uder, Michael; Bogdan, Christian; Luft, Friedrich C.; Titze, Jens

doi:10.1016/j.cmet.2015.02.003

Cited by 279 publications

(398 citation statements)

References 45 publications

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“…AS-48 can be produced in large amounts from industrial fermentation broths at a reasonable cost (62,63) and possesses a very highly stable and compact structure, resistant to exopeptidase degradation, as well as low immunogenicity (32). Furthermore, AS-48 was recently patented as a topical antibacterial agent for skin infections (35), suggesting a relatively easy extrapolation into the ulcers in non-disseminated cutaneous leishmaniasis, inasmuch as AS-48 maintains its activity on high ionic strength, suitable to the hypertonic microenvironment of the skin immune cells (64). Nowadays, the native form of AS-48 is mandatory for its use.…”

Section: Discussionmentioning

confidence: 99%

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Abengózar

Cebrián

Saugar

et al. 2017

Antimicrob Agents Chemother

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We report the feasibility of enterocin AS-48, a circular cationic peptide produced by Enterococcus faecalis, as a new leishmanicidal agent. AS-48 is lethal to Leishmania promastigotes as well as to axenic and intracellular amastigotes at low micromolar concentrations, with scarce cytotoxicity to macrophages. AS-48 induced a fast bioenergetic collapse of L. donovani promastigotes but only a partial permeation of their plasma membrane with limited entrance of vital dyes, even at concentrations beyond its full lethality. Fluoresceinated AS-48 was visualized inside parasites by confocal microscopy and seen to cause mitochondrial depolarization and reactive oxygen species production. Altogether, AS-48 appeared to have a mixed leishmanicidal mechanism that includes both plasma membrane permeabilization and additional intracellular targets, with mitochondrial dysfunctionality being of special relevance. This complex leishmanicidal mechanism of AS-48 persisted even for the killing of intracellular amastigotes, as evidenced by transmission electron microscopy. We demonstrated the potentiality of AS-48 as a new and safe leishmanicidal agent, expanding the growing repertoire of eukaryotic targets for bacteriocins, and our results provide a proof of mechanism for the search of new leishmanicidal bacteriocins, whose diversity constitutes an almost endless source for new structures at moderate production cost and whose safe use on food preservation is well established.

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Section: Discussionmentioning

confidence: 99%

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Abengózar

Cebrián

Saugar

et al. 2017

Antimicrob Agents Chemother

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“…Thus, salt deposition might serve as an ancient mechanism to aid in immune-mediated pathogen removal. 64 …”

Section: T H 1 and T Hmentioning

confidence: 99%

Immune Mechanisms in Arterial Hypertension

Wenzel¹,

Turner²,

Krebs³

et al. 2016

Journal of the American Society of Nephrology

167

148

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Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive endorgan damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

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“…Osmotic stress, associated with systemic infections 43 , is sensed and regulated by the infected host, via several mechanisms including the activation of nuclear factor of activated T cells 5 (NFAT5) 44 (Figure 2). The osmotic stress response regulated by this transcription factor acts in a cytoprotective manner in parenchyma cells 45 , conferring tissue damage control in the kidney during systemic polymicrobial infections 46 and likely in the heart during infection with coxsackievirus 47 in mice ( Figure 2).…”

mentioning

confidence: 99%

Disease tolerance and immunity in host protection against infection

2017

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The immune system has most likely evolved to limit the negative impact exerted by pathogens on host homeostasis. This defense strategy relies on the concerted action of innate and adaptive components of the immune system, which sense and target pathogens for containment, destruction or expulsion. Resistance to infection refers to these immune functions, which reduce the pathogen load of an infected host as the means to preserve homeostasis. Immune-driven resistance to infection is coupled to an additional, and arguably as important, defense strategy that limits the extent of dysfunction imposed to host parenchyma tissues during infection, without exerting a direct negative impact on pathogens.This defense strategy, called disease tolerance, relies on tissue damage control mechanisms that prevent the deleterious effects of pathogens, while uncoupling immunedriven resistance mechanisms from immunopathology and disease. Here we provide a unifying view of resistance and disease tolerance within the framework of immunity to infection.

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Cutaneous Na+ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense

Cited by 279 publications

References 45 publications

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Immune Mechanisms in Arterial Hypertension

Disease tolerance and immunity in host protection against infection

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