Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock

ABSTRACT Sepsis caused by Gram-negative bacteria is the consequence of an unrestrained infection that continuously releases lipopolysaccharide (LPS) into the bloodstream, which triggers an uncontrolled systemic inflammatory response leading to multiorgan failure and death. After scrutinizing the imm...

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Autores principales:	Marcos J. Ramos-Benitez, Caleb Ruiz-Jimenez, Jose J. Rosado-Franco, Willy D. Ramos-Pérez, Loyda B. Mendez, Antonio Osuna, Ana M. Espino
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	CD38 Fasciola hepatica cytokines fatty acid binding protein macrophages septic shock Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cef3d064ad834faaac6cd5b629a2ab13
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spelling	oai:doaj.org-article:cef3d064ad834faaac6cd5b629a2ab132021-11-15T15:22:21ZFh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock10.1128/mSphere.00548-182379-5042https://doaj.org/article/cef3d064ad834faaac6cd5b629a2ab132018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00548-18https://doaj.org/toc/2379-5042ABSTRACT Sepsis caused by Gram-negative bacteria is the consequence of an unrestrained infection that continuously releases lipopolysaccharide (LPS) into the bloodstream, which triggers an uncontrolled systemic inflammatory response leading to multiorgan failure and death. After scrutinizing the immune modulation exerted by a recombinant Fasciola hepatica fatty acid binding protein termed Fh15, our group demonstrated that addition of Fh15 to murine macrophages 1 h prior to LPS stimulation significantly suppresses the expression of proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL1-β). The present study aimed to demonstrate that Fh15 could exert a similar anti-inflammatory effect in vivo using a mouse model of septic shock. Among the novel findings reported in this article, (i) Fh15 suppressed numerous serum proinflammatory cytokines/chemokines when injected intraperitoneally 1 h after exposure of animals to lethal doses of LPS, (ii) concurrently, Fh15 increased the population of large peritoneal macrophages (LPMs) in the peritoneal cavity (PerC) of LPS-injected animals, and (iii) Fh15 downregulated the expression on spleen macrophages of CD38, a cell surface ectoenzyme with a critical role during inflammation. These findings present the first evidence that the recombinant parasitic antigen Fh15 is an excellent modulator of the PerC cell content and in vivo macrophage activation, endorsing Fh15’s potential as a drug candidate against sepsis-related inflammatory response. IMPORTANCE Sepsis is a potentially life-threatening complication of an infection. Sepsis is mostly the consequence of systemic bacterial infections leading to exacerbated activation of immune cells by bacterial products, resulting in enhanced release of inflammatory mediators. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a critical factor in the pathogenesis of sepsis, which is sensed by Toll-like receptor 4 (TLR4). The scientific community highly pursues the development of antagonists capable of blocking the cytokine storm by blocking TLR4. We report here that a recombinant molecule of 14.5 kDa belonging to the Fasciola hepatica fatty acid binding protein (Fh15) is capable of significantly suppressing the LPS-induced cytokine storm in a mouse model of septic shock when administered by the intraperitoneal route 1 h after a lethal LPS injection. These results suggest that Fh15 is an excellent candidate for drug development against endotoxemia.Marcos J. Ramos-BenitezCaleb Ruiz-JimenezJose J. Rosado-FrancoWilly D. Ramos-PérezLoyda B. MendezAntonio OsunaAna M. EspinoAmerican Society for MicrobiologyarticleCD38Fasciola hepaticacytokinesfatty acid binding proteinmacrophagesseptic shockMicrobiologyQR1-502ENmSphere, Vol 3, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD38 Fasciola hepatica cytokines fatty acid binding protein macrophages septic shock Microbiology QR1-502
spellingShingle	CD38 Fasciola hepatica cytokines fatty acid binding protein macrophages septic shock Microbiology QR1-502 Marcos J. Ramos-Benitez Caleb Ruiz-Jimenez Jose J. Rosado-Franco Willy D. Ramos-Pérez Loyda B. Mendez Antonio Osuna Ana M. Espino Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock
description	ABSTRACT Sepsis caused by Gram-negative bacteria is the consequence of an unrestrained infection that continuously releases lipopolysaccharide (LPS) into the bloodstream, which triggers an uncontrolled systemic inflammatory response leading to multiorgan failure and death. After scrutinizing the immune modulation exerted by a recombinant Fasciola hepatica fatty acid binding protein termed Fh15, our group demonstrated that addition of Fh15 to murine macrophages 1 h prior to LPS stimulation significantly suppresses the expression of proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL1-β). The present study aimed to demonstrate that Fh15 could exert a similar anti-inflammatory effect in vivo using a mouse model of septic shock. Among the novel findings reported in this article, (i) Fh15 suppressed numerous serum proinflammatory cytokines/chemokines when injected intraperitoneally 1 h after exposure of animals to lethal doses of LPS, (ii) concurrently, Fh15 increased the population of large peritoneal macrophages (LPMs) in the peritoneal cavity (PerC) of LPS-injected animals, and (iii) Fh15 downregulated the expression on spleen macrophages of CD38, a cell surface ectoenzyme with a critical role during inflammation. These findings present the first evidence that the recombinant parasitic antigen Fh15 is an excellent modulator of the PerC cell content and in vivo macrophage activation, endorsing Fh15’s potential as a drug candidate against sepsis-related inflammatory response. IMPORTANCE Sepsis is a potentially life-threatening complication of an infection. Sepsis is mostly the consequence of systemic bacterial infections leading to exacerbated activation of immune cells by bacterial products, resulting in enhanced release of inflammatory mediators. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a critical factor in the pathogenesis of sepsis, which is sensed by Toll-like receptor 4 (TLR4). The scientific community highly pursues the development of antagonists capable of blocking the cytokine storm by blocking TLR4. We report here that a recombinant molecule of 14.5 kDa belonging to the Fasciola hepatica fatty acid binding protein (Fh15) is capable of significantly suppressing the LPS-induced cytokine storm in a mouse model of septic shock when administered by the intraperitoneal route 1 h after a lethal LPS injection. These results suggest that Fh15 is an excellent candidate for drug development against endotoxemia.
format	article
author	Marcos J. Ramos-Benitez Caleb Ruiz-Jimenez Jose J. Rosado-Franco Willy D. Ramos-Pérez Loyda B. Mendez Antonio Osuna Ana M. Espino
author_facet	Marcos J. Ramos-Benitez Caleb Ruiz-Jimenez Jose J. Rosado-Franco Willy D. Ramos-Pérez Loyda B. Mendez Antonio Osuna Ana M. Espino
author_sort	Marcos J. Ramos-Benitez
title	Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock
title_short	Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock
title_full	Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock
title_fullStr	Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock
title_full_unstemmed	Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock
title_sort	fh15 blocks the lipopolysaccharide-induced cytokine storm while modulating peritoneal macrophage migration and cd38 expression within spleen macrophages in a mouse model of septic shock
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/cef3d064ad834faaac6cd5b629a2ab13
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Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock

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