Humanized mice, a new model to study the influence of drug treatment on neonatal sepsis.

Abstract:

:Bacterial infection with group B Streptococcus (GBS) represents a prominent threat to neonates and fetuses in the Western world, causing severe organ damage and even death. To improve current therapeutic strategies and to investigate new approaches, an appropriate in vivo model to study the immune response of a human immune system is needed. Therefore, we introduced humanized mice as a new model for GBS-induced sepsis. Humanized mice feature deficiencies similar to those found in neonates, such as lower immunoglobulin levels and myeloid cell dysfunction. Due to the husbandry in specific-pathogen-free (SPF) facilities, the human immune cells in these mice also exhibit a naive phenotype which mimics the conditions in fetuses/neonates. Following infection, cytokine release and leukocyte trafficking from the bone marrow to the lymphoid organ (spleen) and into the peritoneum (site of infection) as well as bacterial spreading and clearance were traceable in the humanized mice. Furthermore, we investigated the effects of betamethasone and indomethacin treatment using this novel sepsis model. Although both drugs are commonly used in perinatal care, little is known about their effects on the neonatal immune system. Treatment of infected humanized mice not only induced the reduction of human leukocytes in the spleen but also increased the bacterial load in all analyzed organs, including the brain, which did not show infiltration of live GBS in untreated controls. These studies demonstrate the utility of the humanized mice as a new model to study an immature human immune response during bacterial infection and allow the investigation of side effects induced by various treatments.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Ernst W,Zimara N,Hanses F,Männel DN,Seelbach-Göbel B,Wege AK

doi

10.1128/IAI.01235-12

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

1520-31

issue

5

eissn

0019-9567

issn

1098-5522

pii

IAI.01235-12

journal_volume

81

pub_type

杂志文章
  • A 43-kilodalton pneumococcal surface protein, PspA: isolation, protective abilities, and structural analysis of the amino-terminal sequence.

    abstract::PspA is an antigenically variable surface protein of Streptococcus pneumoniae that appears to be essential for full pneumococcal virulence. In addition, monoclonal antibodies to PspA protect mice against infection with specific strains of pneumococci virulent for mice. In this study, we have isolated the 43-kDa N-term...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.59.4.1285-1289.1991

    authors: Talkington DF,Crimmins DL,Voellinger DC,Yother J,Briles DE

    更新日期:1991-04-01 00:00:00

  • Survival of immunoglobulin G-opsonized Toxoplasma gondii in nonadherent human monocytes.

    abstract::Toxoplasma gondii is a protozoan parasite that is able to penetrate human monocytes by either passive uptake during phagocytosis or active penetration. It is expected that immunoglobulin G (IgG) opsonization will target the parasite to macrophage Fc gamma receptors for phagocytic processing and subsequent degradation....

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.63.11.4290-4294.1995

    authors: Fadul CE,Channon JY,Kasper LH

    更新日期:1995-11-01 00:00:00

  • Inhibition of phagocytosis-associated chemiluminescence by superoxide dismutase.

    abstract::During the process of phagocytosis, human leukocytes emit a burst of luminescence which can be measured in a liquid scintillation spectrometer. The enzyme superoxide dismutase, which removes superoxide anions (O(2.)), inhibited this chemiluminescence by 70% at a concentration of 100 mug/ml. The enzyme did not inhibit ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:

    authors: Webb LS,Keele BB Jr,Johnston RB Jr

    更新日期:1974-06-01 00:00:00

  • Identification of lambda gt11 clones encoding the major antigenic determinants expressed by Theileria parva sporozoites.

    abstract::An antiserum, C16, was raised in cattle against freeze-thawed extracts of sporozoites of Theileria parva (Muguga). This antiserum, which neutralizes sporozoite infectivity in vitro, identified theileria-specific antigens having approximate molecular masses of 105, 90, 85, 69, 67, 52, 47, and 43 kilodaltons (kDa) on We...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.58.6.1828-1834.1990

    authors: Iams KP,Hall R,Webster P,Musoke AJ

    更新日期:1990-06-01 00:00:00

  • A gene, uge, is essential for Klebsiella pneumoniae virulence.

    abstract::Klebsiella pneumoniae strains typically express both smooth lipopolysaccharide (LPS) with O antigen molecules and capsule polysaccharide (K antigen) on the surface. A single mutation in a gene that codes for a UDP galacturonate 4-epimerase (uge) renders a strain with the O-:K- phenotype (lack of capsule and LPS withou...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.72.1.54-61.2004

    authors: Regué M,Hita B,Piqué N,Izquierdo L,Merino S,Fresno S,Benedí VJ,Tomás JM

    更新日期:2004-01-01 00:00:00

  • Detection of specific antibody in adult human periodontitis sera to surface antigens of Bacteroides gingivalis.

    abstract::Sera from adult periodontitis patients were analyzed for antibody activity against surface antigens of Bacteroides gingivalis by immunoblotting analysis. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.55.3.832-834.1987

    authors: Naito Y,Okuda K,Takazoe I

    更新日期:1987-03-01 00:00:00

  • Lipopolysaccharide structure determines ionic and hydrophobic binding of a cationic antimicrobial neutrophil granule protein.

    abstract::Bactericidal activity and binding of a 57,000-dalton cationic antimicrobial neutrophil granule protein (CAP57) are determined by the presence on bacteria of O-antigen polysaccharide chains and the availability of negatively charged groups in the lipid A region, the inner core region, or both regions of lipopolysacchar...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.56.6.1589-1592.1988

    authors: Farley MM,Shafer WM,Spitznagel JK

    更新日期:1988-06-01 00:00:00

  • Th1 and Th2 cell-associated cytokines in experimental visceral leishmaniasis.

    abstract::In experimental Leishmania donovani infection in BALB/c mice, initial susceptibility gives way to T-cell-dependent acquired resistance and eventual control over visceral infection. Since various cytokines appear to underlie the host response to Leishmania infection, we examined infected liver tissue for gene expressio...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.62.3.1058-1063.1994

    authors: Miralles GD,Stoeckle MY,McDermott DF,Finkelman FD,Murray HW

    更新日期:1994-03-01 00:00:00

  • Immunotherapeutic efficacy of bovine colostral immunoglobulins from a hyperimmunized cow against cryptosporidiosis in neonatal mice.

    abstract::Infection with Cryptosporidium parvum, a ubiquitous protozoan parasite of virtually all mammals, can cause mild to severe diarrhea in immunocompetent hosts and life-threatening diarrhea in immunocompromised hosts. Passive immunotherapy of experimentally infected animals and naturally infected humans with hyperimmune b...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.58.9.2962-2965.1990

    authors: Fayer R,Guidry A,Blagburn BL

    更新日期:1990-09-01 00:00:00

  • Nontypeable Haemophilus influenzae strain 2019 produces a biofilm containing N-acetylneuraminic acid that may mimic sialylated O-linked glycans.

    abstract::Previous studies suggested that nontypeable Haemophilus influenzae (NTHI) can form biofilms during human and chinchilla middle ear infections. Microscopic analysis of a 5-day biofilm of NTHI strain 2019 grown in a continuous-flow chamber revealed that the biofilm had a diffuse matrix interlaced with multiple water cha...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.72.7.4249-4260.2004

    authors: Greiner LL,Watanabe H,Phillips NJ,Shao J,Morgan A,Zaleski A,Gibson BW,Apicella MA

    更新日期:2004-07-01 00:00:00

  • Lysosomal enzyme content of Kupffer and endothelial liver cells isolated from germfree and clean conventional rats.

    abstract::Rats kept under germfree conditions showed lower specific lysosomal enzyme activities in liver endothelial cells, but not in Kupffer cells. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.33.2.620-622.1981

    authors: Knook DL,Barkway C,Sleyster EC

    更新日期:1981-08-01 00:00:00

  • The fibrinogen- and fibronectin-binding domains of Staphylococcus aureus fibronectin-binding protein A synergistically promote endothelial invasion and experimental endocarditis.

    abstract::Staphylococcus aureus experimental endocarditis relies on sequential fibrinogen binding (for valve colonization) and fibronectin binding (for endothelial invasion) conferred by peptidoglycan-attached adhesins. Fibronectin-binding protein A (FnBPA) reconciles these two properties--as well as elastin binding--and promot...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00405-08

    authors: Piroth L,Que YA,Widmer E,Panchaud A,Piu S,Entenza JM,Moreillon P

    更新日期:2008-08-01 00:00:00

  • Influence of intranasal immunization with synthetic peptides corresponding to conserved epitopes of M protein on mucosal colonization by group A streptococci.

    abstract::A major virulence factor of group A streptococci is M protein, a surface-exposed fibrillar molecule of which there exist more than 80 distinct serological types. Antigenic variability resides largely in the amino-terminal region of M protein, whereas the carboxy-terminal half of the molecule is highly conserved among ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.56.10.2666-2672.1988

    authors: Bessen D,Fischetti VA

    更新日期:1988-10-01 00:00:00

  • Terminal electron transport in Treponema pallidum.

    abstract::Reduced-minus-oxidized difference spectra of sonically treated virulent Treponema pallidum disclosed cytochromes of the b anc c types as well as large amounts of flavoprotein. Difference spectra of the carbon monoxide-binding pigment identified cytochrome o as the terminal oxidase. Physiological reduction of the cytoc...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.16.3.885-890.1977

    authors: Lysko PG,Cox CD

    更新日期:1977-06-01 00:00:00

  • Outer membrane protein expression profile in Helicobacter pylori clinical isolates.

    abstract::The gram-negative gastric pathogen Helicobacter pylori is equipped with an extraordinarily large set of outer membrane proteins (OMPs), whose role in the infection process is not well understood. The Hop (Helicobacter outer membrane porins) and Hor (Hop-related proteins) groups constitute a large paralogous family con...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00364-09

    authors: Odenbreit S,Swoboda K,Barwig I,Ruhl S,Borén T,Koletzko S,Haas R

    更新日期:2009-09-01 00:00:00

  • Characterization and immunogenicity of the CagF protein of the cag pathogenicity island of Helicobacter pylori.

    abstract::Helicobacter pylori infection causes severe gastroduodenal diseases in humans. Its virulence is strongly increased by the presence of the cag pathogenicity island (cag PAI). It has been shown that CagA, a major antigen in humans, is translocated to the host cell via a secretion system encoded by the cag PAI. The roles...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.70.11.6468-6470.2002

    authors: Seydel A,Tasca E,Berti D,Rappuoli R,Del Giudice G,Montecucco C

    更新日期:2002-11-01 00:00:00

  • Gender is a major factor in determining the severity of mycoplasma respiratory disease in mice.

    abstract::Gender is a significant factor in determining the susceptibility to and severity of pulmonary diseases in both humans and animals. Murine respiratory mycoplasmosis (MRM), due to Mycoplasma pulmonis infection, is an excellent animal model for evaluation of the role of various host factors on the development of acute or...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.69.5.2865-2871.2001

    authors: Yancey AL,Watson HL,Cartner SC,Simecka JW

    更新日期:2001-05-01 00:00:00

  • Clearance of Serratia marcescens from Lungs of Normal Mice.

    abstract::After aerosol deposition of Serratia marcescens in mice, initial delayed pulmonary clearance was followed between 4 and 24 hr later by progressive elimination. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.3.1.187-188.1971

    authors: Southern PM,Pierce AK,Sanford JP

    更新日期:1971-01-01 00:00:00

  • Variations in the ospB gene of Borrelia burgdorferi result in differences in monoclonal antibody reactivity and in production of escape variants.

    abstract::An escape variant of Borrelia burgdorferi, selected with a monoclonal antibody to OspB, expressed a truncated form of OspB, the result of point mutations in the ospB gene leading to a premature termination codon. A single amino acid position in the C terminus of OspB was critical for monoclonal antibody recognition. T...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.62.1.303-307.1994

    authors: Coleman JL,Rogers RC,Rosa PA,Benach JL

    更新日期:1994-01-01 00:00:00

  • Porphyromonas gingivalis infection in pregnant mice is associated with placental dissemination, an increase in the placental Th1/Th2 cytokine ratio, and fetal growth restriction.

    abstract::Our previous animal studies showed that maternal Porphyromonas gingivalis infection in a subcutaneous chamber is associated with hepatic and uterine translocation, as well as systemic induction of maternal inflammatory responses, both of which were associated with fetal growth restriction (FGR). However, P. gingivalis...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.71.9.5163-5168.2003

    authors: Lin D,Smith MA,Elter J,Champagne C,Downey CL,Beck J,Offenbacher S

    更新日期:2003-09-01 00:00:00

  • Secretory leukocyte protease inhibitor interferes with uptake of lipopolysaccharide by macrophages.

    abstract::Macrophages are among the most sensitive targets of bacterial endotoxin (LPS), responding to minute amounts of LPS by releasing a battery of inflammatory mediators. Transfection of macrophages with secretory leukocyte protease inhibitor (SLPI) renders these cells refractory to LPS stimulation. Here we show that uptake...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.67.9.4485-4489.1999

    authors: Ding A,Thieblemont N,Zhu J,Jin F,Zhang J,Wright S

    更新日期:1999-09-01 00:00:00

  • The Mycobacterium tuberculosis phagosome in human macrophages is isolated from the host cell cytoplasm.

    abstract::Knowledge of whether Mycobacterium tuberculosis resides within a relatively impermeable membrane-bound vacuole or is free within the cytoplasm within its host cell is central to an understanding of the immunobiology of this intracellular parasite but is a matter of controversy. To explore this issue, we assessed the a...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.70.10.5800-5807.2002

    authors: Clemens DL,Lee BY,Horwitz MA

    更新日期:2002-10-01 00:00:00

  • Biochemical and immunological characterization of deoxythymidine kinase of thymidine kinaseless HeLa cells biochemically transformed by herpes simplex virus type.

    abstract::Thymidine kinase (TK) from herpes simplex virus type 1 (HSV-1) biochemically transformed HeLa cells, purified by affinity chromatography, has been characterized with respect to its electrophoretic mobility, molecular weight, activation energy, substrate specificity, and immunological specificity. TK purified from HSV-...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.16.2.486-492.1977

    authors: Cheng YC,Chadha KC,Hughes RG Jr

    更新日期:1977-05-01 00:00:00

  • In vitro sensitivity of oral, gram-negative, facultative bacteria to the bactericidal activity of human neutrophil defensins.

    abstract::Neutrophils play a major role in defending the periodontium against infection by oral, gram-negative, facultative bacteria, such as Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga spp. We examined the sensitivity of these bacteria to a mixture of low-molecular-weight peptides and highly p...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.58.12.3934-3940.1990

    authors: Miyasaki KT,Bodeau AL,Ganz T,Selsted ME,Lehrer RI

    更新日期:1990-12-01 00:00:00

  • Bacteroides gingivalis vesicles bind to and aggregate Actinomyces viscosus.

    abstract::Isolated Bacteroides gingivalis 2561 vesicles aggregated suspensions of Actinomyces viscosus and Actinomyces naeslundii of all taxonomy clusters. Vesicles bound near A. viscosus cell walls and among its surface fibrils. Tritiated vesicles bound slightly better to saliva-coated hydroxyapatite (SHA) than to SHA coated w...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.57.5.1618-1620.1989

    authors: Ellen RP,Grove DA

    更新日期:1989-05-01 00:00:00

  • Virulence of the Melioidosis Pathogen Burkholderia pseudomallei Requires the Oxidoreductase Membrane Protein DsbB.

    abstract::The naturally antibiotic-resistant bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a disease with stubbornly high mortality and a complex, protracted treatment regimen. The worldwide incidence of melioidosis is likely grossly underreported, though it is known to be highly endemic in northern...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00938-17

    authors: McMahon RM,Ireland PM,Sarovich DS,Petit G,Jenkins CH,Sarkar-Tyson M,Currie BJ,Martin JL

    更新日期:2018-04-23 00:00:00

  • A Point Mutation in carR Is Involved in the Emergence of Polymyxin B-Sensitive Vibrio cholerae O1 El Tor Biotype by Influencing Gene Transcription.

    abstract::Antimicrobial peptides play an important role in host defense against Vibrio cholerae Generally, the V. cholerae O1 classical biotype is polymyxin B (PB) sensitive and El Tor is relatively resistant. Detection of classical biotype traits like the production of classical cholera toxin and PB sensitivity in El Tor strai...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00080-20

    authors: Samanta P,Mandal RS,Saha RN,Shaw S,Ghosh P,Dutta S,Ghosh A,Imamura D,Morita M,Ohnishi M,Ramamurthy T,Mukhopadhyay AK

    更新日期:2020-04-20 00:00:00

  • C2 toxicity in extract of Clostridium botulinum type C spores.

    abstract::Toxic protein(s) neutralized with anti-C2 toxic serum was extracted from Clostridium botulinum type C spores treated with an alkaline mercaptoethanol solution. C2 toxicity in the spores was located in the spore coat fraction and was more heat stable than that found in culture fluid. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.41.2.858-860.1983

    authors: Yamakawa K,Nishida S,Nakamura S

    更新日期:1983-08-01 00:00:00

  • Neutrophils from Both Susceptible and Resistant Mice Efficiently Kill Opsonized Listeria monocytogenes.

    abstract::Inbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacterium Listeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (polymorphonuclear leukocytes [PMN]) were particularly import...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00085-18

    authors: Pitts MG,Combs TA,D'Orazio SEF

    更新日期:2018-03-22 00:00:00

  • Actinobacillus actinomycetemcomitans serotype b-specific polysaccharide antigen stimulates production of chemotactic factors and inflammatory cytokines by human monocytes.

    abstract::Serotype b-specific polysaccharide antigen (SPA) was extracted from whole cells of Actinobacillus actinomycetemcomitans Y4 by autoclaving and purified by chromatography on DEAE-Sephadex A-25 and Sephacryl S-300. SPA induced the release of monocyte and leukocyte chemotactic factors by human monocytes. Polymyxin B had a...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.64.7.2563-2570.1996

    authors: Yamaguchi N,Yamashita Y,Ikeda D,Koga T

    更新日期:1996-07-01 00:00:00