bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Activation of mRNA of Intercellular Adhesion Molecule 1 and Induction of Its Cell Surface Expression in Normal Human Gingival Fibroblasts byMycoplasma salivariumandMycoplasma fermentans
Authors: Dong Li , Shibata Ken-Ichiro , Sawa Yoshihiko , Hasebe Akira , Yamaoka Yuji , Yoshida Shigemitsu , Watanabe Tsuguo 
Published: December 2019

ABSTRACTLipoproteins in the cell membranes of bothMycoplasma salivariumandMycoplasma fermentanswere demonstrated to trigger the transcription of intercellular adhesion molecule-1 mRNA in normal fibroblasts isolated from human gingival tissue and to induce its cell surface expression by a mechanism distinct from that ofEscherichia colilipopolysaccharide. The lipid moiety of the lipoproteins was suggested to play a key role in the expression of the activity.
Macrophages and Epithelial Cells Respond Differently to the
Pseudomonas aeruginosa
Type III Secretion System
Authors: Coburn Jenifer , Frank Dara W. 
Published: December 2019

ABSTRACT

The multiple effects of
Pseudomonas aeruginosa
type III secretion have largely been attributed to variations in cytotoxin expression between strains. Here we show that the target cell type is also important. While lung epithelial cells showed significant changes in morphology but not viability when infected with
P. aeruginosa
, macrophages were efficiently killed by
P. aeruginosa
. Both responses were dependent on the type III secretion system.
Genetic Characterization of Wild-Type and Mutant
fur
Genes of
Bordetella avium
Authors: Murphy Erin R. , Dickenson Amy , Militello Kevin T. , Connell Terry D. 
Published: December 2019

ABSTRACT

For most, if not all, organisms, iron (Fe) is an essential element. In response to the nutritional requirement for Fe, bacteria evolved complex systems to acquire the element from the environment. The genes encoding these systems are often coordinately regulated in response to the Fe concentration. Recent investigations revealed that
Bordetella avium
, a respiratory pathogen of birds, expressed a number of Fe-regulated genes (T. D. Connell, A. Dickenson, A. J. Martone, K. T. Militello, M. J. Filiatraut, M. L. Hayman, and J. Pitula, Infect. Immun. 66:3597–3605, 1998). By using manganese selection on an engineered strain of
B. avium
that carried an Fe-regulated alkaline phosphatase reporter gene, a mutant was obtained that was affected in expression of Fe-regulated genes. To determine if Fe-dependent regulation in
B. avium
was mediated by a
fur
-like gene, a fragment of the
B. avium
chromosome, corresponding to the
fur
locus of
B. pertussis
, was cloned by PCR. Sequencing revealed that the fragment from
B. avium
encoded a polypeptide with 92% identity to the Fur protein of
B. pertussis
. In vivo experiments showed that the cloned gene complemented H1780, a
fur
mutant of
Escherichia coli
. Southern hybridizations and PCRs demonstrated that the manganese mutant had a deletion of 2 to 3 kbp of nucleotide sequence in the region located immediately 5′ of the
fur
open reading frame. A spontaneous PCR-derived mutant of the
B. avium fur
gene was isolated that encoded a Fur protein in which a histidine was substituted for an arginine at amino acid position 18 (R18H). Genetic analysis showed that the R18H mutant gene when cloned into a low-copy-number vector did not complement the
fur
mutation in H1780. However, the R18H mutant gene was able to complement the
fur
mutation when cloned into a high-copy-number vector. The cloned wild-type
fur
gene will be useful as a genetic tool to identify Fur-regulated genes in the
B. avium
chromosome.
Experimental Lyme Arthritis in the Absence of Interleukin-4 or Gamma Interferon
Authors: Brown Charles R. , Reiner Steven L. 
Published: December 2019

ABSTRACTGenetic resistance and susceptibility to experimental Lyme arthritis have been linked with the production of interleukin-4 (IL-4) or gamma interferon (IFN-γ), respectively. To determine the absolute requirement for these cytokines in disease outcome, we compared arthritis development in wild-type, IL-4-deficient (IL-4°), and IFN-γ-deficient (IFN-γ°) mice. While susceptible C3H mice developed swelling of ankle joints during the second week of infection, this swelling was exacerbated in C3H IFN-γ° mice. Their arthritis severity scores at day 21, however, were similar. Resolution of arthritis was also similar between C3H and C3H IFN-γ° mice. Arthritis-resistant DBA mice did not develop ankle swelling during the experimental period. There were no differences in ankle swelling or arthritis severity scores between control DBA mice and DBA IL-4° mice at any of the time points tested. While the presence of spirochetes in various tissues was similar among all strains at day 21, DBA IL-4° mice had a higher presence of spirochetes in blood, heart, and spleen than the DBA, C3H, and C3H IFN-γ° mice did at day 60. DBA IL-4° mice also had impaired ability to produceBorrelia-specific antibody responses, especially immunoglobulin G1. Thus, while IFN-γ and IL-4 are not absolutely required for arthritis susceptibility or resistance, the production of IL-4 does appear to play an important role inBorrelia-specific antibody production and spirochete clearance.
Interleukin-10 Responses to Liver-Stage Antigen 1 Predict Human Resistance toPlasmodium falciparum
Authors: Kurtis Jonathan D. , Lanar David E. , Opollo Malachi , Duffy Patrick E. 
Published: December 2019

ABSTRACTThe design of an effective vaccine againstPlasmodium falciparum, the most deadly malaria parasite of humans, requires a careful definition of the epitopes and the immune responses involved in protection. Liver-stage antigen 1 (LSA-1) is specifically expressed during the hepatic stage ofP. falciparumand elicits cellular and humoral immune responses in naturally exposed individuals. We report here that interleukin-10 (IL-10) production in response to LSA-1 predicts resistance toP. falciparumafter eradication therapy. Resistance was not related to gamma interferon or tumor necrosis factor alpha production. This is the first report that human IL-10 responses are associated with resistance after eradication therapy, and our findings support the inclusion of LSA-1 in a vaccine against malaria.
Pretreatment with Granulocyte Colony-Stimulating Factor Attenuates the Inflammatory Response but Not the Bacterial Load in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits
Authors: Østergaard Christian , Benfield Thomas , Gesser Borbola , Kharazmi Arsalan , Frimodt-Møller Niels , Espersen Frank , Lundgren Jens D. 
Published: December 2019

ABSTRACTA possible immunomodulatory role of granulocyte colony-stimulating factor (G-CSF) was investigated in an experimental pneumococcal meningitis model in rabbits. Animals were pretreated with G-CSF (10 μg/kg subcutaneously twice a day) starting 48 h before in vivo and ex vivo experiments, causing a five- to six-fold increase in the peripheral leukocyte level. Meningitis was induced by intracisternal inoculation of ∼4 × 105CFU ofStreptococcus pneumoniaetype 3. Neutrophil pleocytosis and interleukin-8 (IL-8) levels were significantly attenuated in G-CSF-pretreated animals compared to untreated animals (P< 0.05). Furthermore, G-CSF pretreatment significantly delayed alterations in cerebrospinal fluid (CSF) tumor necrosis factor alpha and IL-1β levels, as well as protein and glucose levels (P< 0.05). No difference in CSF bacterial concentrations was found, whereas the blood bacterial concentration was significantly decreased in G-CSF-pretreated animals (P< 0.05). Ex vivo chemotaxis of neutrophils isolated from G-CSF-pretreated animals was significantly decreased compared to that of neutrophils from untreated animals (P< 0.05). In conclusion, G-CSF pretreatment attenuates meningeal inflammation and enhances systemic bacterial killing. Further preclinical studies are required to investigate whether this may affect the clinical course of meningitis and thus whether G-CSF treatment may have a beneficial role in pneumococcal meningitis.
Vaccination against Shigellosis with Attenuated
Shigella flexneri
2a Strain SC602
Authors: Coster Trinka S. , Hoge Charles W. , VanDeVerg Lillian L. , Hartman Antoinette B. , Oaks Edwin V. , Venkatesan Malabi M. , Cohen Dani , Robin Guy , Fontaine-Thompson Annick , Sansonetti Philippe J. , Hale Thomas L. 
Published: December 2019

ABSTRACT

The
Shigella flexneri
2a SC602 vaccine candidate carries deletions of the plasmid-borne virulence gene
icsA
(mediating intra- and intercellular spread) and the chromosomal locus
iuc
(encoding aerobactin) (S. Barzu, A. Fontaine, P. J. Sansonetti, and A. Phalipon, Infect. Immun. 64:1190–1196, 1996). Dose selection studies showed that SC602 causes shigellosis in a majority of volunteers when 3 × 10
8
or 2 × 10
6
CFU are ingested. In contrast, a dose of 10
4
CFU was associated with transient fever or mild diarrhea in 2 of 15 volunteers. All volunteers receiving single doses of ≥10
4
CFU excreted
S. flexneri
2a, and this colonization induced significant antibody-secreting cell and enzyme-linked immunosorbent assay responses against
S. flexneri
2a lipopolysaccharide in two-thirds of the vaccinees. Seven volunteers who had been vaccinated 8 weeks earlier with a single dose of 10
4
CFU and 7 control subjects were challenged with 2 × 10
3
CFU of virulent
S. flexneri
2a organisms. Six of the control volunteers developed shigellosis with fever and severe diarrhea or dysentery, while none of the vaccinees had fever, dysentery, or severe symptoms
(P
= 0.005). Three vaccinees experienced mild diarrhea, and these subjects had lower antibody titers than did the fully protected volunteers. Although the apparent window of safety is narrow, SC602 is the first example of an attenuated
S. flexneri
2a candidate vaccine that provides protection against shigellosis in a stringent, human challenge model.
Differential Sensitivity of Human Epithelial Cells to
Pseudomonas aeruginosa
Exoenzyme S
Authors: McGuffie Eileen M. , Fraylick Jennifer E. , Hazen-Martin Debra J. , Vincent Timothy S. , Olson Joan C. 
Published: December 2019

ABSTRACT

Exoenzyme S (ExoS) is an ADP-ribosyltransferase produced and directly translocated into eukaryotic cells by the opportunistic pathogen
Pseudomonas aeruginosa
. Model systems that allow bacterial translocation of ExoS have found ExoS to have multiple effects on eukaryotic cell function, affecting DNA synthesis, actin cytoskeletal structure, and cell matrix adherence. To understand mechanisms underlying differences observed in cell sensitivities to ExoS, we examined the effects of bacterially translocated ExoS on multiple human epithelial cell lines. Of the cell lines examined, confluent normal kidney (NK) epithelial cells were most resistant to ExoS, while tumor-derived cell lines were highly sensitive to ExoS. Analysis of the mechanisms of resistance indicated that cell association as well as an intrinsic resistance to morphological alterations were associated with increased resistance to ExoS. Conversely, increased sensitivity to ExoS appeared to be linked to epithelial cell growth, with tumor cells capable of undergoing non-contact-inhibited, anchorage-independent growth all being sensitive to ExoS, and NK cells becoming sensitive to ExoS when subconfluent and growing. Consistent with the possibility that growth-related, actin-based structures are involved in sensitivity to ExoS, scanning electron microscopy revealed cellular extensions from sensitive, growing cells to bacteria, which were not readily evident in resistant cells. In all studies, the severity of effects of ExoS on cell function directly correlated with the degree of Ras modification, indicating that sensitivity to ExoS in some manner related to the efficiency of ExoS translocation and its ADP-ribosylation of Ras. Our results suggest that factors expressed by growing epithelial cells are required for the bacterial contact-dependent translocation of ExoS; as normal epithelial cells differentiate into polarized confluent monolayers, expression of these factors is altered, and cells in turn become more resistant to the effects of ExoS.
Protective Immunity of Microsphere-Based Mucosal Vaccines against Lethal Intranasal Challenge withStreptococcus pneumoniae
Authors: Seong Seung-Yong , Cho Nam-Hyuk , Kwon Ick Chan , Jeong Seo Young 
Published: December 2019

ABSTRACTMucosal vaccination of capsular polysaccharide (PS) ofStreptococcus pneumoniaeand subsequent creation of the first line of immunological defense in mucosa were examined. Mucosal as well as systemic antibody responses to PS were evoked by peroral or intranasal immunization of BALB/c mice with PS-cholera toxin B subunit (CTB) conjugates entrapped in the alginate microspheres (AM). The bacterial colonization at the lung mucosa was most profoundly inhibited (<95%) by intranasal immunization with the naked conjugate (PS-CTB). The mice vaccinated orally with encapsulated conjugate [AM(PS-CTB)] showed significant reduction on the level of pneumococcal bacteremia (<99%). Eighty percent of the mice perorally immunized with AM (PS-CTB) were protected from lethal intranasal challenge withS. pneumoniae, whereas more than 60% of the mice in the other control groups died of infection. Our novel approach may prove to be important in the development of a mucosal vaccine that will provide protection of mucosal surfaces of host.
CD4+T Cells Which React to theLeishmania majorLACK Antigen Rapidly Secrete Interleukin-4 and Are Detrimental to the Host in Resistant B10.D2 Mice
Authors: Julia Valérie , Glaichenhaus Nicolas 
Published: December 2019

ABSTRACTLeishmania majorinduces the rapid production of interleukin-4 (IL-4) in both susceptible BALB/c and resistant B10.D2 mice. In both strains, IL-4 is produced by T cells which react to the parasite LACK (forLeishmaniahomolog of the receptor for activated C kinase) antigen. The rapid production of IL-4 in B10.D2 mice does not confer susceptibility but results in increased parasite burdens.
Antibody-Based Protection of Gnotobiotic Piglets Infected with
Escherichia coli
O157:H7 against Systemic Complications Associated with Shiga Toxin 2
Authors: Donohue-Rolfe Art , Kondova Ivanela , Mukherjee Jean , Chios Kerry , Hutto David , Tzipori Saul 
Published: December 2019

ABSTRACT

Hemolytic-uremic syndrome (HUS) is a serious disease in children, attributable in the majority of cases to infection with Shiga toxin (Stx)-producing
Escherichia coli
. Using gnotobiotic piglets orally infected with
E. coli
O157:H7, which develop Stx-related cerebellar lesions and fatal neurological symptoms, we show that administration of Stx2-specific antiserum well after challenge protected, in a dose-response fashion, against these symptoms for at least 24 h after bacterial challenge. Twenty-six of 30 piglets given Stx2 antiserum survived the challenge, compared to only 4 of 16 animals given control serum or saline. Given our observations in piglets, Stx antibody of human origin may likewise prevent HUS in children.
Chlamydial Colonization of Multiple Mucosae following Infection by Any Mucosal Route
Authors: Perry Linda L. , Hughes Scott 
Published: December 2019

ABSTRACTChlamydia trachomatisinoculated by any mucosal route colonized multiple murine mucosae and, in most cases, the spleen, liver, and kidneys. Cell-to-cell transmission, systemic dissemination, and autoinoculation of infectious fluids may have contributed to chlamydial spread. Intermucosal trafficking of protective T cells cannot be accurately evaluated by using live chlamydial challenges.
Immunostimulatory DNA as an Adjuvant in Vaccination againstLeishmania major
Authors: Stacey Katryn J. , Blackwell Jenefer M. 
Published: December 2019

ABSTRACTOligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against leishmaniasis. To test this, susceptible BALB/c mice were vaccinated with soluble leishmanial antigen (SLA) with or without CpG ODN as adjuvant and then challenged withLeishmania majormetacyclic promastigotes. CpG ODN alone gave partial protection when injected up to 5 weeks prior to infection, and longer if the ODN was bound to alum. To demonstrate an antigen-specific adjuvant effect, a minimum of 6 weeks between vaccination and infection was required. Subcutaneous administration of SLA alone, SLA plus alum, or SLA plus non-CpG ODN resulted in exacerbated disease compared to unvaccinated mice. Mice receiving SLA plus CpG ODN showed a highly significant (P< 5 × 10−5) reduction in swelling compared to SLA-vaccinated mice and enhanced survival compared to unvaccinated mice. The modulation of the response to SLA by CpG ODN was maintained even when mice were infected 6 months after vaccination. CpG ODN was not an effective adjuvant for antibody production in response to SLA unless given together with alum, when it promoted production of immunoglobulin G2a, a Th1-associated isotype. Our results suggest that with an appropriate antigen, CpG ODN would provide a stable, cost-effective adjuvant for use in vaccination against leishmaniasis.
Loss of Resistance to Ingestion and Phagocytic Killing by O−and K−Mutants of a UropathogenicEscherichia coliO75:K5 Strain
Authors: Burns Stacy M. , Hull Sheila I. 
Published: December 2019

ABSTRACTTo determine the importance of the O75 O antigen and the K5 capsular antigen in resistance to phagocytosis and phagocytic killing, we used previously described O75−and K5−mutants from an O75+K5+wild-type uropathogenicEscherichia colistrain in phagocytosis assays with polymorphonuclear leukocytes (PMNs) and monocytes. At a 10-to-1 ratio of bacteria to phagocytes and in the presence of 10% serum, the parental strain GR-12 was resistant to both PMNs and monocytes over a 2-h incubation period. The O75−and K5−mutants were similar in sensitivity to killing by both PMNs and monocytes, decreasing in viability by 80% in the first hour. Yet, a significant difference in killing between the O75−and K5−mutants was observed in the first 15 min of incubation. The K5−mutant decreased in numbers by almost 60%, while the O75−mutant increased in numbers similarly to GR-12 in the first 15 min. The difference in killing was found not to be due to the rate of opsonization. To further determine the mechanism of resistance, a fluorescence assay was used to differentiate attached and internalized bacteria. The K5 capsule hindered the association of both the wild-type strain and the O75−mutant in the initial incubation time with PMNs. In conclusion, both the K5 capsule and O75 O antigen play crucial roles in resistance to phagocytosis over time.
Prior Immunity to Homologous and Heterologous
Salmonella
Serotypes Suppresses Local and Systemic Anti-Fragment C Antibody Responses and Protection from Tetanus Toxin in Mice Immunized with
Salmonella
Strains Expressing Fragment C
Authors: Roberts Mark , Bacon Andrew , Li Jingli , Chatfield Steven 
Published: December 2019

ABSTRACT

We have investigated the effect of preexisting immunity to homologous (
Salmonella typhimurium
) or heterologous (
S. dublin
) serotypes of
Salmonella
on the ability of an attenuated
S. typhimurium aroA aroD
vector (BRD509) to immunize mice against the heterologous antigen fragment C (FrgC). We studied two strains, BRD847 and BRD937, expressing FrgC carried on plasmids that differ only with respect to the promoter controlling FrgC expression, the
nirB
promoter in the case of BRD847 and the
htrA
promoter in the case of BRD937. Mice were preimmunized orally with
S. typhimurium
BRD509,
S. dublin aroA aroD
(BRD620), or saline. Forty-four days later, they were immunized orally with BRD847 or BRD937. Prior immunity to
S. typhimurium
severely depressed the serum immunoglobulin G (IgG) and IgA anti-FrgC response in both BRD847- and BRD937-immunized mice. Mice with existing immunity to
S. dublin
also had lower IgG anti-FrgC geometric mean titers (GMTs) than did mice preimmunized with saline, but this difference was significant only in the case of mice immunized with BRD937. However, in nonimmune mice or in mice preimmunized with
S. typhimurium
or
S. dublin
, the anti-FrgC IgG GMTs were always higher in mice in the BRD937 groups than in the equivalent BRD847 groups. This is reflected in the effect of prior immunity on the ability of oral immunization with BRD847 or BRD937 to protect mice from challenge with a lethal dose of tetanus toxin. All of the mice preimmunized with saline and then immunized with BRD847 or BRD937 survived challenge. Only 20% of the animals immunized with BRD847 and 60% of the mice in the BRD937 group survived tetanus toxin challenge if they were preimmunized with BRD509. Preexisting immunity to
S. dublin
did not affect the ability of BRD937 to immunize mice against tetanus, but it did reduce the efficiency of BRD847: only 60% percent of the mice survived challenge. The intestinal secretory IgA responses to FrgC were very similar in the BRD847 and BRD937 groups. Prior immunity did depress the IgA anti-FrgC titers but only significantly so in the mice preimmunized with BRD509. These results show that preexisting
Salmonella
immunity, particularly to homologous serotypes, can severely compromise the ability of live
Salmonella
vectors to deliver heterologous antigens to the mammalian immune system. However, the results also indicate that this may be overcome by the design of more powerful in vivo expression systems.
Selective Distribution of a High-Affinity Plasminogen-Binding Site among Group A Streptococci Associated with Impetigo
Authors: Svensson Mikael D. , Sjöbring Ulf , Bessen Debra E. 
Published: December 2019

ABSTRACTGroup A streptococci can be classified according to their tendency to cause either impetigo, pharyngitis, or both types of infection. Genotypic markers for tissue site preference lie withinemmgenes, which encode fibrillar surface proteins that play a key role in virulence.emmgene products (M and M-like proteins) display an extensive array of binding activities for tissue and plasma proteins of the human host. In a previous study, a high-affinity binding site for human plasmin(ogen) was mapped to theemm53gene product. In this report, a structurally similar plasminogen-binding domain is found to be widely and selectively distributed among group A streptococci harboring theemmgene marker for the skin as the preferred tissue site for infection. The findings are highly suggestive of a central role for bacterial modulation of host plasmin(ogen) during localized infection at the epidermis.