Abstract:
:Polymicrobial intra-abdominal infections (IAIs) are a significant cause of morbidity and mortality, particularly when fungal pathogens are involved. Our experimental murine model of IAI involving intraperitoneal inoculation of Candida albicans and Staphylococcus aureus results in synergistic lethality (∼80%) due to exacerbated inflammation. Monomicrobial infection results in no mortality, despite a microbial burden and dissemination similar to those in a coinfection. In the coinfection model, the immunomodulatory eicosanoid prostaglandin E2 (PGE2) was determined to be necessary and sufficient to induce mortality, implicating PGE2 as the central mediator of the amplified inflammatory response. The aim of this study was to identify key components of the PGE2 biosynthetic and signaling pathway involved in the inflammatory response and explore whether these can be targeted to prevent or reduce mortality. Using selective pharmacological inhibitors of cyclooxygenases (COX) or PGE2 receptor antagonists in the C. albicans-S. aureus IAI mouse model, we found that inhibition of COX and/or blocking of PGE2 receptor 1 (EP1) or PGE2 receptor 3 (EP3) signaling reduced proinflammatory cytokine production, promoted interleukin-10 production, reduced cellular damage in the peritoneal cavity, and, most importantly, significantly improved survival. The greatest effect on survival was obtained by the simultaneous inhibition of COX-1 activity and EP1 and EP3 receptor signaling. Importantly, early inhibition of PGE2 pathways dramatically improved the survival of fluconazole-treated mice compared with that achieved with fluconazole treatment alone. These findings indicate that COX-1 and the EP1 and EP3 receptors mediate the downstream pathological effects of PGE2 during polymicrobial IAI and may serve as effective therapeutic targets.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Ikeh MAC,Fidel PL Jr,Noverr MCdoi
10.1128/IAI.00144-18subject
Has Abstractpub_date
2018-06-21 00:00:00issue
7eissn
0019-9567issn
1098-5522pii
IAI.00144-18journal_volume
86pub_type
杂志文章abstract::Although protective immunity in C57BL/6 mice induced by a single dose of the radiation-attenuated schistosome vaccine is believed to be mediated by Th1-type immune responses, we here report that in BALB/c mice protection can also depend upon signaling via the interleukin-4 (IL-4) receptor which conventionally governs ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.1.228-236.2001
更新日期:2001-01-01 00:00:00
abstract::Lipopolysaccharide (LPS) binding protein (LBP) is an acute-phase protein that enhances the responsiveness of immune cells to LPS by virtue of its capacity to transfer LPS to CD14. To determine the role of LBP in the innate immune response to peritonitis, LBP gene-deficient (LBP(-/-)) and normal wild-type mice were int...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.71.12.6747-6753.2003
更新日期:2003-12-01 00:00:00
abstract::The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to th...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00153-17
更新日期:2017-07-19 00:00:00
abstract::The suppression of T-cell deoxyribonucleic acid (DNA) synthesis by serum from mice acutely with murine cytomegalovirus (MCMV) was investigated. Spleen cells from uninfected mice were exposed to concanavalin A in the presence of serum taken from mice at various times after infection with MCMV. The capacity of the serum...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.17.2.378-381.1977
更新日期:1977-08-01 00:00:00
abstract::Antiprotein monoclonal antibodies derived from mice inoculated with Rickettsia rickettsii heated at 56 degrees C for 15 min are of two types: one is type specific for epitopes denatured by moderate temperatures, and the other is specific for epitopes resistant to 100 degrees C for 5 min. The heat-resistant epitopes ar...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.3.825-827.1987
更新日期:1987-03-01 00:00:00
abstract::The adherence of Enterococcus faecalis strains to human T24 cells was examined by scanning electron microscopy. Five highly adhesive strains were identified from 30 strains isolated from the urine of patients with urinary tract infections. No efficiently adhesive strains were found among the 30 strains isolated from t...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsu...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00088-09
更新日期:2009-07-01 00:00:00
abstract::Legionella pneumophila was susceptible to the antimicrobial action of oxygen metabolites generated by both the myeloperoxidase-H(2)O(2)-halide and the xanthine oxidase systems. ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.39.1.487-489.1983
更新日期:1983-01-01 00:00:00
abstract::The response of ferrets after intranasal inoculation of inactivated A/Hong Kong/68 (H3N2) influenza virus vaccines is reported. Normal ferrets given either saline vaccine in drops or freeze-dried vaccine in an aerosol intranasally did not produce detectable serum or nasal hemagglutination inhibiting antibody and were ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.9.6.985-990.1974
更新日期:1974-06-01 00:00:00
abstract::Recurrent urinary tract infections (UTIs) are a significant clinical problem for many women; however, host susceptibility factors have not been completely defined. The mouse model of induced UTI provides an experimental environment in which to identify specific host characteristics that are important in initial bacter...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.6.2798-2802.1998
更新日期:1998-06-01 00:00:00
abstract::It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium. Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all. Binding occurred only to C. alb...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.50.2.598-600.1985
更新日期:1985-11-01 00:00:00
abstract::Previous passive antibody transfer experiments have indicated that immunity to a 46-kilodalton membrane glycoprotein (M-2) of Leishmania amazonensis may protect against infection with this parasite. In the studies described in this paper, we investigated the ability of the purified M-2 molecule to elicit a protective ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.12.3272-3279.1988
更新日期:1988-12-01 00:00:00
abstract::Obligate vacuolar pathogens produce proteins that localize to the host cell-derived membranes of the vacuoles in which they reside, yielding unique organelles that are optimally suited for pathogen survival. Anaplasma phagocytophilum is an obligate vacuolar bacterium that infects neutrophils and causes the emerging an...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01418-09
更新日期:2010-05-01 00:00:00
abstract::Salmonella choleraesuis chi 3781, an attenuated [delta cya-12 delta(crp-cdt)19] mutant, was electroporated with the plasmid pBA31-R7, which codes for the expression of a 31-kDa protein from Brucella abortus (BCSP31). Recombinant S. choleraesuis chi 3781 stably maintained the pBA31-R7 plasmid and continued to express t...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.2.610-618.1993
更新日期:1993-02-01 00:00:00
abstract::We have previously shown that splenocytes from mice acutely infected with Trypanosoma cruzi exhibit high levels of nitric oxide (NO)-mediated apoptosis. In the present study, we used the gamma interferon (IFN-gamma)-knockout (IFN-gamma(-/-)) mice to investigate the role of IFN-gamma in modulating apoptosis induction a...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.8.3864-3871.1999
更新日期:1999-08-01 00:00:00
abstract::Previous research in this laboratory, using photoactivatable radioiodinated lipopolysaccharide derivatized with sulfosuccinimidyl-2-(p-azidosalicylamide)-1,3'-dithiopropionate (125I-ASD-LPS), has resulted in the identification of a specific LPS receptor with a molecular mass of approximately 73 kDa on murine lymphocyt...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.3.845-852.1992
更新日期:1992-03-01 00:00:00
abstract::In vitro experimentation indicates that periodontitis-associated bacteria contain potent polyclonal B-cell activators (PBA). We reasoned that if PBA were operative in vivo, plasma cells specific for nonoral antigens should be present in the inflamed gingival tissues, which are characterized by a plasma cell infiltrate...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.4.823-830.1988
更新日期:1988-04-01 00:00:00
abstract::Brucellosis is a bacterial disease of animals and humans. Brucella abortus barely activates the innate immune system at the onset of infection, and this bacterium is resistant to the microbicidal action of complement. Since complement stands as the first line of defense during bacterial invasions, we explored the role...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00567-18
更新日期:2018-09-21 00:00:00
abstract::Ambient pH signaling involves a cascade of conserved Rim or Pal products in ascomycetous yeasts or filamentous fungi, respectively. Recent evidences in the fungi Aspergillus nidulans, Saccharomyces cerevisiae, Yarrowia lipolytica, and Candida albicans suggested that components of endosomal sorting complexes required f...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.12.7977-7987.2005
更新日期:2005-12-01 00:00:00
abstract::In the presence of temporary obstruction (20 h), ascending Escherichia coli urinary infection leads to irreversible acute exudative pyelonephritis (AEP) in rats. The purpose of the present study was to investigate the early inflammatory events which take place in response to the presence of bacteria in the kidney pare...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.40.2.529-533.1983
更新日期:1983-05-01 00:00:00
abstract::Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence t...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00345-16
更新日期:2016-09-19 00:00:00
abstract::Influenza A/Scotland/74 (H3N2) and A/Victoria/75 (H3N2) cold-adapted (ca) recombinant viruses, prepared by mating the A/Ann Arbor/6/60 (H2N2) ca donor virus and influenza A wild-type virus, were evaluated in adult seronegative volunteers (serum hemagglutination-inhibiting antibody titer, =1:8) for level of attenuati...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.23.2.253-259.1979
更新日期:1979-02-01 00:00:00
abstract::Lipid X, a precursor in the biosynthesis of lipid A, has been claimed to possess most of the immunostimulatory activity but none of the toxicity of endotoxin. However, recent work shows that synthetic lipid X can be contaminated with small amounts of N,O-acylated disaccharide-1-phosphate (H. Aschauer, A. Grob, J. Hild...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.7.2351-2358.1991
更新日期:1991-07-01 00:00:00
abstract::Metastatic infection after hematogenous dissemination of Candida species is presumably dependent on the fungus traversing the vascular endothelium. An in vitro model of the earliest events of metastatic Candida infection was developed with whole vascular strips. Freshly obtained porcine blood vessels were secured in a...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.42.1.374-384.1983
更新日期:1983-10-01 00:00:00
abstract::Numerous investigations have shown that 70-kDa heat shock protein (Hsp70) homologs interact tightly with hydrophobic proteins and functionally assist proteins in membranous organelles and environments. One such protein is the Chlamydia trachomatis Hsp70 that is associated with isolated outer membrane complexes of infe...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.70.2.535-543.2002
更新日期:2002-02-01 00:00:00
abstract::Dentilisin is a major surface protease and virulence factor of the bacterium Treponema denticola. In this study, we found that T. denticola reduced inflammatory cytokines, including interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha, in peripheral blood mononuclear cells through degradation by dentili...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.74.4.2462-2467.2006
更新日期:2006-04-01 00:00:00
abstract::Macrophage ribonucleic acid (RNA) synthesis is an important metabolic process intimately related to the function of these cells. Mouse peritoneal macrophage RNA was extracted with phenol in the presence of bentonite and electrophoresed on composite agarose-polyacrylamide gels. The pulse-chase technique was used to fol...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.13.6.1531-1538.1976
更新日期:1976-06-01 00:00:00
abstract::Bordetella pertussis adenylate cyclase-hemolysin (AC-Hly), encoded by the cyaA gene, belongs to the RTX family of toxins with extensive glycine-rich repeats in the carboxy-terminal portion. AC-Hly possesses both adenylate cyclase toxic and hemolytic activities that depend on a posttranslational modification mediated b...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.9.3583-3589.1993
更新日期:1993-09-01 00:00:00
abstract::A 10-amino-acid repeating sequence of the hemagglutinating portion of Clostridium difficile toxin A has been synthesized and used to produce antisera in rabbits. Antipeptide antibody inhibited toxin A-mediated hemagglutination and neutralized cytotoxic activity. Immunoblot analysis with the antipeptide antibody reveal...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.9.3151-3155.1991
更新日期:1991-09-01 00:00:00
abstract::A procedure was developed to purify dermonecrotic toxin (DNT) from a sonic extract of a serotype D strain of Pasteurella multocida. Sonic extract containing DNT was applied to a DEAE-Sephacel column and eluted by a linear gradient of NaCl. Upon rechromatographing, fractions with dermonecrotic activity for guinea pigs ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.46.2.429-434.1984
更新日期:1984-11-01 00:00:00