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.
journal_name
mSpherejournal_title
mSphereauthors
Ramos-Benitez MJ,Ruiz-Jimenez C,Rosado-Franco JJ,Ramos-Pérez WD,Mendez LB,Osuna A,Espino AMdoi
10.1128/mSphere.00548-18subject
Has Abstractpub_date
2018-12-19 00:00:00issue
6issn
2379-5042pii
3/6/e00548-18journal_volume
3pub_type
杂志文章相关文献
mSphere文献大全abstract::Coxsackievirus typically infects humans via the gastrointestinal tract, which has a large number of microorganisms collectively referred to as the microbiota. To study how the intestinal microbiota influences enteric virus infection, several groups have used an antibiotic regimen in mice to deplete bacteria. These stu...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00632-18
更新日期:2019-02-20 00:00:00
abstract::Skin and soft tissue infections (SSTIs) are common in the general population, with increased prevalence among military trainees. Previous research has revealed numerous nasal microbial signatures that correlate with SSTI development and Staphylococcus aureus colonization. Thus, we hypothesized that the ecology of the ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00232-16
更新日期:2016-10-05 00:00:00
abstract::Human adenoviruses (HAdV), species D in particular (HAdV-D), are frequently associated with epidemic keratoconjunctivitis (EKC). Although the infection originates at the ocular surface epithelium, the mechanisms by which HAdV-Ds bypass the membrane-associated mucin (MAM)-rich glycocalyx of the ocular surface epitheliu...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00112-15
更新日期:2016-02-10 00:00:00
abstract::Malaria is a devastating illness that causes approximately 500,000 deaths annually. The malaria-causing parasite (Plasmodium genus) uses the process of translational repression to regulate its growth, development, and transmission. As poly(A)-binding proteins (PABP) have been identified as critical components of RNA m...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00435-17
更新日期:2018-01-10 00:00:00
abstract::Syndiniales are a ubiquitous group of protist parasites that infect and kill a wide range of hosts, including harmful bloom-forming dinoflagellates. Despite the importance of parasitism as an agent of plankton mortality, parasite-host dynamics remain poorly understood, especially over time, hindering the inclusion of ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00209-20
更新日期:2020-05-27 00:00:00
abstract::The extraintestinal pathogenic Escherichia coli (ExPEC) H30 subclone of sequence type 131 (ST131-H30) has emerged abruptly as a dominant lineage of ExPEC responsible for human disease. The ST131-H30 lineage has been well described phylogenetically, yet its plasmid complement is not fully understood. Here, single-molec...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00121-16
更新日期:2016-06-29 00:00:00
abstract::The oral periodontopathic bacterium Fusobacterium nucleatum has been repeatedly associated with colorectal tumors. Molecular analysis has identified specific virulence factors that promote tumorigenesis in the colon. However, other oral community members, such as members of the Porphyromonas spp., are also found with ...
journal_title:mSphere
pub_type: 杂志文章,评审
doi:10.1128/mSphere.00102-16
更新日期:2016-05-11 00:00:00
abstract::The major surface lipophosphoglycan (LPG) of Leishmania parasites is critical to vector competence in restrictive sand fly vectors in mediating Leishmania attachment to the midgut epithelium, considered essential to parasite survival and development. However, the relevance of LPG for sand flies that harbor multiple sp...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00594-20
更新日期:2020-09-09 00:00:00
abstract::We describe a novel genome integration system that enables the introduction of DNA fragments as large as 50 kbp into the chromosomes of recipient bacteria. This system, named BPI, comprises a bacterial artificial chromosome vector and phage-derived gene integration machinery. We introduced the wbm locus of Bordetella ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00417-17
更新日期:2018-01-24 00:00:00
abstract::Many microbiologists exhibit a fascination with unculturable bacteria. This intrigue can be expressed through curiosity about nutrient needs, as well as about parameters such as optimal temperature, oxygen levels, minimum and optimal light, or other such environmental factors. Microbiologists study organisms' genetic ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.01046-20
更新日期:2020-10-28 00:00:00
abstract::Cryptococcus neoformans is a pathogenic yeast that causes lethal cryptococcal meningitis in immunocompromised patients. One of the challenges in treating cryptococcosis is the development of resistance to azole antifungals. Previous studies linked azole resistance to elevated numbers of copies of critical resistance g...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00205-17
更新日期:2017-06-14 00:00:00
abstract::Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiment...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00254-17
更新日期:2017-08-09 00:00:00
abstract::Grf10, a homeodomain-containing transcription factor, regulates adenylate and one-carbon metabolism and morphogenesis in the human fungal pathogen Candida albicans Here, we identified functional domains and key residues involved in transcription factor activity using one-hybrid and mutational analyses. We localized ac...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00467-18
更新日期:2018-10-24 00:00:00
abstract::In fungi, most metabolic processes are subject to regulation by light. Trichoderma reesei is adapted to degradation of plant cell walls and regulates production of the required enzymes in a manner dependent on the nutrient source and the light status. Here we investigated the interrelated relevance of two regulation l...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00089-17
更新日期:2017-05-10 00:00:00
abstract::Amino acids participate in several critical processes in the biology of trypanosomatids, such as osmoregulation, cell differentiation, and host cell invasion. Some of them provide reducing power for mitochondrial ATP synthesis. It was previously shown that alanine, which is formed mainly by the amination of pyruvate, ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphereDirect.00338-18
更新日期:2018-07-18 00:00:00
abstract::Père David's deer (Elaphurus davidianus or milu) is an endangered species, and the prevalence of antimicrobial resistance (AMR) such as mcr-1-positive strains among them has been unknown. In this study, we aimed to investigate the genomic characterizations of mcr-1-positive strains and provide insight into the dissemi...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.01221-20
更新日期:2020-12-23 00:00:00
abstract::Bifidobacterium species are important commensals capable of dominating the infant gut microbiome, in part by producing acids that suppress growth of other taxa. Bifidobacterium species are less prone to possessing antimicrobial resistance (AMR) genes (ARGs) than other taxa that may colonize infants. Given that AMR is ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00441-18
更新日期:2018-09-26 00:00:00
abstract::The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that re...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00376-16
更新日期:2017-03-29 00:00:00
abstract::[This corrects the article DOI: 10.1128/mSphere.00393-18.]. ...
journal_title:mSphere
pub_type: 已发布勘误
doi:10.1128/mSphere.00535-18
更新日期:2018-10-10 00:00:00
abstract::The acquisition of genetic material conferring the arsenal necessary for host virulence is a prerequisite on the path to becoming a plant pathogen. More subtle mutations are also required for the perception of cues signifying the presence of the target host and optimal conditions for colonization. The decision to acti...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00367-16
更新日期:2017-03-01 00:00:00
abstract::In densely populated urban environments, the distribution of microbes and the drivers of microbial community assemblages are not well understood. In sprawling metropolitan habitats, the "urban microbiome" may represent a mix of human-associated and environmental taxa. Here we carried out a baseline study of automated ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00226-16
更新日期:2016-11-16 00:00:00
abstract::The fungal pathogen Candida glabrata can cause both mucosal and disseminated infections. Cell adhesion, a key step in colonization and infection, depends in C. glabrata primarily on the Epa family of cell adhesion proteins. While Epa proteins have been documented to mediate specific adhesion to host glycans, some of t...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00277-19
更新日期:2019-05-01 00:00:00
abstract::Outbreaks of infection occur more often than they are reported in most developing countries, largely due to poor diagnostic services. A Klebsiella species bacteremia outbreak in a newborn unit with high mortality was recently encountered at a location being surveilled for childhood bacteremia. These surveillance effor...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00685-18
更新日期:2019-03-13 00:00:00
abstract::Botulinum neurotoxins (BoNTs), produced by neurotoxigenic clostridial species, are the cause of the severe disease botulism in humans and animals. Early research on BoNTs has led to their classification into seven serotypes (serotypes A to G) based upon the selective neutralization of their toxicity in mice by homolog...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00100-15
更新日期:2016-02-24 00:00:00
abstract::Infections by malaria parasites can lead to very different clinical outcomes, ranging from mild symptoms to death. Differences in the ability of the spleen to deal with the infected red blood cells (iRBCs) are linked to differences in virulence. Using virulent and avirulent strains of the rodent malaria parasite Plasm...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00018-15
更新日期:2015-12-09 00:00:00
abstract::This study examines the pharmacodynamics of antimicrobials that are used to treat Salmonella with each other and with key components of the innate immune system. Antimicrobial synergy was assessed using time-kill and checkerboard assays. Antimicrobial interactions with innate immunity were studied by employing catheli...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00410-17
更新日期:2017-12-06 00:00:00
abstract::Toxoplasma gondii can infect and replicate in vascular endothelial cells prior to entering host tissues. However, little is known about the molecular interactions at the parasite-endothelial cell interface. We demonstrate that T. gondii infection of primary human umbilical vein endothelial cells (HUVEC) altered cell m...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00550-19
更新日期:2020-01-29 00:00:00
abstract::Escherichia coli populations undergo repeated replacement of parental genotypes with fitter variants deep in stationary phase. We isolated one such variant, which emerged after 3 weeks of maintaining an E. coli K-12 population in stationary phase. This variant displayed a small colony phenotype and slow growth and was...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00092-20
更新日期:2020-04-15 00:00:00
abstract::Parasitic protozoans of the genus Theileria are intracellular pathogens that induce the cellular transformation of leukocytes, causing uncontrolled proliferation of the infected host cell. The transforming stage of the parasite has a strictly intracellular lifestyle and ensures its distribution to both daughter cells ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00709-19
更新日期:2020-02-05 00:00:00
abstract::Feedback mechanisms are fundamental to the control of physiological responses. One important example in gene regulation, termed negative autoregulation (NAR), occurs when a transcription factor (TF) inhibits its own production through transcriptional repression. This enables more-rapid homeostatic control of gene expr...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00718-20
更新日期:2020-08-19 00:00:00