bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eukaryotic Cell Uptake of Heparin-Coated Microspheres: a Model of Host Cell Invasion by
Chlamydia trachomatis
Authors: Stephens Richard S. , Fawaz Farah S. , Kennedy Kathleen A. , Koshiyama Kelly , Nichols Barbara , van Ooij Christiaan , Engel Joanne N. 
Published: July 2002

ABSTRACT

Using polystyrene microspheres coated with heparin or heparan sulfate, it was shown that coated microspheres specifically bound eukaryotic cells and were endocytosed by nonprofessional phagocytic cells. Coated microspheres displayed properties of binding to eukaryotic cells that were similar to those of chlamydiae, and the microspheres were competitively inhibited by chlamydial organisms. Endocytosis of heparin-coated beads resulted in the tyrosine phosphorylation of a similar set of host proteins as did endocytosis of chlamydiae; however, unlike viable chlamydial organisms, which prevent phagolysosomal fusion, endocytosed beads were trafficked to a lysosomal compartment. These findings suggest that heparin-coated beads and
Chlamydia trachomatis
enter eukaryotic cells by similar pathways.
Cloning of PorcineNRAMP1and Its Induction by Lipopolysaccharide, Tumor Necrosis Factor Alpha, and Interleukin-1β: Role of CD14 and Mitogen-Activated Protein Kinases
Authors: Zhang Guolong , Wu Hua , Ross Christopher R. , Minton J. Ernest , Blecha Frank 
Published: July 2002

ABSTRACTThe gene for natural resistance-associated macrophage protein 1 (NRAMP1) plays a dominant role in controlling the resistance of inbred mice to infection with intracellular bacteria, such asMycobacteria,Salmonella, andLeishmania. NRAMP1 is a membrane protein with a consensus transport motif present in one of the intracellular loops. Although its functions remain unclear, recent clues suggest that NRAMP1 protein plays a potential role in ion transport, which presumably accounts for the ability of this single protein to regulate the intraphagosomal replication of several species of antigenically unrelated intracellular pathogens. Expression ofNRAMP1in mice can be induced by lipopolysaccharide (LPS) or bacterial infection; however, little is known about the mechanisms of induction. Here, we report the cloning of the full-length cDNA for porcineNRAMP1, which had over 85% identity in amino acid sequence to its congeners from humans, mice, cattle, and sheep. As for its mammalian congeners, expression of porcineNRAMP1mRNA was cell and tissue specific and was highest in macrophages. Investigation of the molecular mechanisms by whichNRAMP1is induced showed that LPS-induced expression in macrophages, neutrophils, and peripheral blood mononuclear cells was time and dose dependent and was mediated primarily through CD14. Induction ofNRAMP1required de novo protein synthesis, and mitogen-activated protein kinases (MAPK) were essential. Blockage of either p38 or p42/44 MAPK pathways suppressed the expression ofNRAMP1to basal levels. These findings suggest that bacterial infection and proinflammatory mediators induceNRAMP1expression via activation of MAPK pathways.
Iron Acquisition fromPseudomonas aeruginosaSiderophores by Human Phagocytes: an Additional Mechanism of Host Defense through Iron Sequestration?
Authors: Britigan Bradley E. , Rasmussen George T. , Olakanmi Oyebode , Cox Charles D. 
Published: July 2002

ABSTRACTChelation of iron to iron-binding proteins is a strategy of host defense. Some pathogens counter this via the secretion of low-molecular-weight iron-chelating agents (siderophores). Human phagocytes possess a high-capacity mechanism for iron acquisition from low-molecular-weight iron chelates. Efficient acquisition and sequestration of iron bound to bacterial siderophores by host phagocytes could provide a secondary mechanism to limit microbial access to iron. In the present work we report that human neutrophils, macrophages, and myeloid cell lines can acquire iron from the twoPseudomonas aeruginosasiderophores. Analogous to iron acquisition from other low-molecular-weight chelates, iron acquisition from the siderophores is ATP independent, induced by multivalent cationic metals, and unaffected by inhibitors of endocytosis and pinocytosis. In vivo, this process could serve as an additional mechanism of host defense to limit iron availability to invading siderophore-producing microbes.
Polymorphonuclear Neutrophils Are Necessary for the Recruitment of CD8+T Cells in the Liver in a Pregnant Mouse Model ofChlamydophila abortus(Chlamydia psittaciSerotype 1) Infection
Authors: de Oca Roberto Montes , Buendía Antonio J. , Del Río Laura , Sánchez Joaquín , Salinas Jesús , Navarro Jose A. 
Published: July 2002

ABSTRACTThe role of polymorphonuclear neutrophils (PMNs) in the development of the specific immune response againstChlamydophila abortus(Chlamydia psittaciserotype 1) infection was studied in a pregnant mouse model involving treatment with RB6-8C5 monoclonal antibody. PMN depletion significantly affected the immune response in the liver, in which the T-lymphocyte and F4/80+cell populations decreased, particularly the CD8+T-cell population. A Th1-like response, characterized by high levels of gamma interferon without detectable levels of interleukin 4 (IL-4) in serum, was observed in both depleted and nondepleted mice, although an increased production of IL-10 was detected in the depleted group. Our results suggest that PMNs play a very important role in the recruitment of other leukocyte populations to the inflammatory foci but have little influence in the polarization of the immune specific response toward a Th1-like response.
In Situ Analysis of the Evolution of the Primary Immune Response in MurineChlamydia trachomatisGenital Tract Infection
Authors: Morrison Sandra G. , Morrison Richard P. 
Published: July 2002

ABSTRACTAdaptive immune responses contribute to the resolution ofChlamydia trachomatisgenital tract infection and protect against reinfection, but our understanding of the mechanisms of those protective responses is incomplete. In this study, we analyzed by in situ immunohistochemistry the progression of the inflammatory and cytokine responses in the genital tracts of mice vaginally infected withC. trachomatisstrain mouse pneumonitis. The cellular inflammatory response was characterized by an initial elevation in myeloid cells in the vagina (day 3) and uterine horns (day 7), followed by a marked rise in the number of T cells, predominantly CD4+cells. CD8+T cells and CD45R+B cells were also detected but were much less numerous. Perivascular clusters of CD4+T cells, which resembled clusters of T cells seen in delayed-type hypersensitivity responses, were evident by 2 weeks postinfection. Following the resolution of infection, few CD8+T cells and CD45R+B cells remained, whereas numerous CD4+T cells and perivascular clusters of CD4+T cells persisted in genital tract tissues. Interleukin-12 (IL-12)- and tumor necrosis factor alpha (TNF-α)-producing cells were observed in vaginal tissue by day 3 of infection and in uterine tissues by day 7. Cells producing IL-4 or IL-10 were absent from vaginal tissues at day 3 of infection but were present in uterine tissues by day 7 and were consistently more numerous than IL-12- and TNF-α-producing cells. Thus, the evolution of the local inflammatory response was characterized by the accumulation of CD4+T cells into perivascular clusters and the presence of cells secreting both Th1- and Th2-type cytokines. The persistence of CD4+-T-cell clusters long after infection had resolved (day 70) may provide for a readily mobilizable T-cell response by which previously infected animals can quickly respond to and control a secondary infectious challenge.
Immunization with Parasite-Derived Apical Membrane Antigen 1 or Passive Immunization with a Specific Monoclonal Antibody Protects BALB/c Mice against Lethal
Plasmodium yoelii yoelii
YM Blood-Stage Infection
Authors: Narum David L. , Ogun Solabomi A. , Thomas Alan W. , Holder Anthony A. 
Published: July 2002

ABSTRACT

We have purified apical merozoite antigen 1 (AMA-1) from extracts of red blood cells infected with the rodent malaria parasite
Plasmodium yoelii yoelii
YM. When used to immunize mice, the protein induced a strong protective response against a challenge with the parasite. Monoclonal antibodies specific for
P. yoelii yoelii
AMA-1 were prepared, and one was very effective against the parasite on passive immunization. A second protein that appears to be located in the apical rhoptry organelles and associated with AMA-1 was identified.
Interleukin-7 or Interleukin-15 Enhances Survival ofMycobacterium tuberculosis-Infected Mice
Authors: Maeurer Markus J. , Trinder Peter , Hommel Gerhard , Walter Wolfgang , Freitag Kirsten , Atkins Derek , Störkel Stefan 
Published: July 2002

ABSTRACTBoth antigen-presenting cells and immune effector cells are required to effectively eradicate or containMycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive “cross talk” between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of α/β and γ/δ T cells. Here we show that either cytokine is able to enhance survival ofM. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival could be achieved only when IL-7 or IL-15 was delivered as a treatment (i.e., 3 weeks postinfection), not when it was administered at the time of infection. Increased survival ofM. tuberculosis-infected animals was observed following passive transfer of spleen cells harvested fromM. tuberculosis-infected, IL-7- or IL-15-treated animals, but not after transfer of spleen cells obtained from mice which received either cytokine alone. Histological examination revealed that IL-7 and IL-15 failed to significantly impact on the number and composition of granulomas formed or the bacterial load. Our data indicated that administration of IL-7 or IL-15 toM. tuberculosis-treated animals resulted in a qualitatively different cellular immune response in spleen cells as reflected by increased tumor necrosis factor alpha and decreased gamma interferon secretion in response toM. tuberculosis-infected antigen-presenting cells.
Immunization of Mice with Combinations of Pneumococcal Virulence Proteins Elicits Enhanced Protection against Challenge with
Streptococcus pneumoniae
Authors: Ogunniyi A. David , Folland Rebekah L. , Briles David E. , Hollingshead Susan K. , Paton James C. 
Published: July 2002

ABSTRACT

The vaccine potential of a combination of three pneumococcal virulence proteins was evaluated in an active-immunization–intraperitoneal-challenge model in BALB/c mice, using very high challenge doses of
Streptococcus pneumoniae
. The proteins evaluated were a genetic toxoid derivative of pneumolysin (PdB), pneumococcal surface protein A (PspA), and a 37-kDa metal-binding lipoprotein referred to as PsaA. Mice immunized with individual proteins or combinations thereof were challenged with high doses of virulent type 2 or type 4 pneumococci. The median survival times for mice immunized with combinations of proteins, particularly PdB and PspA, were significantly longer than those for mice immunized with any of the antigens alone. A similar effect was seen in a passive protection model. Thus, combinations of pneumococcal proteins may provide the best non-serotype-dependent protection against
S. pneumoniae
.
Priming withChlamydia trachomatisMajor Outer Membrane Protein (MOMP) DNA followed by MOMP ISCOM Boosting Enhances Protection and Is Associated with Increased Immunoglobulin A and Th1 Cellular Immune Responses
Authors: Dong-Ji Zhang , Yang Xi , Shen Caixia , Lu Hong , Murdin Andrew , Brunham Robert C. 
Published: July 2002

ABSTRACTWe previously reported that DNA vaccination was able to elicit cellular immune responses and partial protection againstChlamydia trachomatisinfection. However, DNA immunization alone did not generate immune responses or protection as great as that induced by using live organisms. In this study, we evaluated the immunologic effects of a combinational vaccination approach usingC. trachomatismouse pneumonitis (MoPn) major outer membrane protein (MOMP) DNA priming followed by boosting with immune-stimulating complexes (ISCOM) of MOMP protein (MOMP ISCOM) for protection of BALB/c mice against MoPn lung infection. Substantially better protection to challenge infection was observed in mice given combinational vaccination compared with mice given MOMP ISCOM immunization alone, and the protection approximated that induced by live organisms. Enhanced protection was correlated with stronger delayed-type hypersensitivity, higher levels of gamma interferon production, and increased immunoglobulin A antibody responses in lung homogenates. The results indicate that DNA priming followed by ISCOM protein boosting may be useful in designing a fully protective chlamydial vaccine.
The Abundant Larval Transcript-1 and -2 Genes ofBrugia malayiEncode Stage-Specific Candidate Vaccine Antigens for Filariasis
Authors: Gregory William F. , Atmadja Agnes K. , Allen Judith E. , Maizels Rick M. 
Published: July 2002

ABSTRACTLymphatic filariasis is a major tropical disease caused by the mosquito-borne nematodesBrugiaandWuchereria. About 120 million people are infected and at risk of lymphatic pathology such as acute lymphangitis and elephantiasis. Vaccines against filariasis must generate immunity to the infective mosquito-derived third-stage larva (L3) without accentuating immunopathogenic responses to lymphatic-dwelling adult parasites. We have identified two highly expressed genes, designated abundant larval transcript-1 and -2 (alt-1andalt-2), from each of which mRNAs account for >1% of L3 cDNAs. ALT-1 and ALT-2 share 79% amino acid identity across 125 residues, including a putative signal sequence and a prominent acidic tract. Expression ofalt-1andalt-2is initiated midway through development in the mosquito, peaking in the infective larva and declining sharply following entry into the host. Humans exposed toBrugia malayishow a high frequency of immunoglobulin G1 (IgG1) and IgG3 antibodies to ALT-1 and -2, distinguishing them from adult-stage antigens, which are targeted by the IgG4 isotype. Immunization of susceptible rodents (jirds) with ALT-1 elicited a 76% reduction in parasite survival, the highest reported for a single antigen from any filarial parasite. ALT-1 and the closely related ALT-2 are therefore strong candidates for a future vaccine against human filariasis.
Toll-Like Receptor 4-Deficient Mice Have Reduced Bone Destruction following Mixed Anaerobic Infection
Authors: Hou Linda , Sasaki Hajime , Stashenko Philip 
Published: July 2002

ABSTRACTC3H/HeJ mice have an impaired ability to respond to lipopolysaccharide (LPS) due to a mutation in the gene that encodesToll-like receptor 4 (TLR4). The effect of TLR4 deficiency on host responses to endodontic infections is unknown. In the present study, we compared periapical bone destruction, sepsis, and inflammatory cytokine production in LPS-hyporesponsive C3H/HeJ and wild-type control C3H/HeOuJ mice. The mandibular first molars of both strains were subjected to pulpal exposure and infection with a mixture of four anaerobic pathogens,Prevotella intermedia,Fusobacterium nucleatum,Streptococcus intermedius, andPeptostreptococcus micros. At sacrifice on day 21, TLR4-deficient C3H/HeJ mice had significantly reduced periapical bone destruction compared to wild-type C3H/HeOuJ mice (P< 0.001). The decreased bone destruction in C3H/HeJ correlated with reduced expression of the bone resorptive cytokines interleukin 1α (IL-1α) (P< 0.01) and IL-1β (P< 0.05) as well as the proinflammatory cytokine IL-12 (P< 0.05). No significant differences were seen in the levels of gamma interferon, tumor necrosis factor alpha (TNF-α), or IL-10 between the two strains. The expression of IL-1α, IL-1β, TNF-α, IL-10, and IL-12 were all significantly reduced in vitro in macrophages from both TLR4-deficient C3H/HeJ and C57BL/10ScNCr strains, compared to wild-type controls. Notably, the responses of TLR4-deficient macrophages to both gram-positive and gram-negative bacteria were similarly reduced. Neither C3H/HeJ nor C3H/HeOuJ mice exhibited orofacial abscess development or infection dissemination as determined by splenomegaly or cachexia. We conclude that intact TLR function mediates increased proinflammatory responses and bone destruction in response to mixed anaerobic infections.
Mucosal Defense against Gastrointestinal Nematodes: Responses of Mucosal Mast Cells and Mouse Mast Cell Protease 1 during PrimaryStrongyloides venezuelensisInfection in FcRγ-Knockout Mice
Authors: Onah Denis N. , Uchiyama Fukumi , Nagakui Yuuko , Ono Masao , Takai Toshiyuki , Nawa Yukifumi 
Published: July 2002

ABSTRACTA possible role for the γ subunit of immunoglobulin Fc receptors (FcR) in mucosal defenses against intestinal nematode parasites was studied using age-matched FcRγ-knockout (FcRγ−/−) and wild-type (FcRγ+/+) C57BL/6 mice. Mice were infected subcutaneously with 3,000 infective larvae ofStrongyloides venezuelensis, and the degree of infection was monitored by daily fecal egg counts and adult worm recovery on days 8 and 13 postinfection. Mucosal mast cell (MMC) responses were assayed by in situ intestinal mast cell counts in stained histological sections of the jejunum and by measuring mouse mast cell protease 1 (MMCP-1) release in serum using sandwich enzyme-linked immunosorbent assay. FcRγ−/−mice had significantly higher egg counts (P< 0.01) and numbers of adult worms (P< 0.05) than FcRγ+/+mice, but mastocytosis and serum MMCP-1 release were comparable. It was concluded that MMCP-1 release may be spontaneous, does not depend on mast cell degranulation via the FcRγ signaling system, and appears to play no role in the expulsion ofS. venezuelensis. The delay in worm expulsion in the FcRγ−/−mice might be related to inability of the MMC to degranulate and release effector molecules other than MMCP-1, since FcRγ deletion abrogates mast cell degranulative responses.
Shigella flexneri
LuxS Quorum-Sensing System Modulates
virB
Expression but Is Not Essential for Virulence
Authors: Day William A. , Maurelli Anthony T. 
Published: July 2002

ABSTRACT

Quorum-sensing systems regulate the expression of virulence factors in a wide variety of plant and animal pathogens, including members of the
Enterobacteriaceae
. Studies of
Shigella
virulence gene expression have demonstrated that maximal expression of genes encoding the type III secretion system and its substrates and maximal activity of this virulence organelle occur at high cell density. In these studies, we demonstrate that the expression of
ipa
,
mxi
, and
spa
invasion operons is maximal in stationary-phase bacteria and that conditioned media derived from stationary-phase cultures enhance the expression of these loci. In contrast, expression of
virB
, a transcription factor essential for the expression of invasion loci, peaks in late log phase; accordingly,
virB
expression is enhanced by a signal(s) present in conditioned media derived from late-log-phase cultures. Autoinducer 2 (AI-2), a quorum signaling molecule active in late log phase, was synthesized by
Shigella
species and enteroinvasive
Escherichia coli
and shown to be responsible for the observed peak of
virB
expression. However, AI-2 does not influence invasion operon expression and is not required for
Shigella
virulence, as mutants deficient in AI-2 synthesis are fully virulent. The implications of these findings with regard to both
virB
and invasion operon expression and the evolution of circuitries governing virulence gene expression are discussed.
Role of Genetic Resistance in Invasive Pneumococcal Infection: Identification and Study of Susceptibility and Resistance in Inbred Mouse Strains
Authors: Gingles Neill A. , Alexander Janet E. , Kadioglu Aras , Andrew Peter W. , Kerr Alison , Mitchell Timothy J. , Hopes Elaine , Denny Paul , Brown Steve , Jones Huw B. , Little Steve , Booth George C. , McPheat William L. 
Published: July 2002

ABSTRACTFrom a panel of nine inbred mice strains intranasally infected withStreptococcus pneumoniaetype 2 strain, BALB/c mice were resistant and CBA/Ca and SJL mice were susceptible to infection. Further investigation revealed that BALB/c mice were able to prevent proliferation of pneumococci in the lungs and blood, whereas CBA/Ca mice showed no bacterial clearance. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca but not BALB/c mice. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 h postinfection. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice, and there was a greater cellular infiltration into the lung tissue of BALB/c mice at the earlier time points. Our data suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils.
Increase of γδ T Lymphocytes in Murine Lungs Occurs during Recovery from Pulmonary Infection byNocardia asteroides
Authors: Tam Stanley , King Donald P. , Beaman Blaine L. 
Published: July 2002

ABSTRACTPrevious studies have demonstrated that γδ T lymphocytes are important for host resistance to pulmonary infection of the murine lung by log-phase cells ofNocardia asteroides. To study the role of γδ T cells in nocardial interactions in the murine lung, C57BL/6J wild type and C57BL/6J-Tcrd (γδ T-cell knockout mice) were infected intranasally with log-phase cells ofN. asteroidesGUH-2. At 3, 5, and 7 days after infection, the γδ T cells were quantified by multiparameter flow cytometry. At the same time, Gram and hematoxylin-eosin stains of paraffin sections were performed to monitor the host responses. The data showed that γδ T lymphocytes increased significantly within the lungs after intranasal infection, and the peak of this cellular increase occurred at 5 days. Furthermore, at this time, greater than 50% of the CD3 T-cell receptor (TCR)-positive (CD3+) cells were γδ TCR positive. Histological examination clearly showed divergent inflammatory responses in the lungs of wild-type mice compared to γδ T-cell knockout mice. The C57BL/6J-Tcrd mice were less capable of clearing the organism, and the polymorphonuclear leukocyte response lasted longer than in wild-type C57BL/6J mice. These results showed that γδ T cells were actively involved in modulating the innate host responses to murine pulmonary infection byN. asteroides.
Tuberculosis Contacts but Not Patients Have Higher Gamma Interferon Responses to ESAT-6 than Do Community Controls in The Gambia
Authors: Vekemans Johan , Lienhardt Christian , Sillah Jackson S. , Wheeler Jeremy G. , Lahai George P. , Doherty Mark T. , Corrah Tumani , Andersen Peter , McAdam Keith P. W. J. , Marchant Arnaud 
Published: July 2002

ABSTRACT

The
Mycobacterium tuberculosis
antigen ESAT-6 has been proposed for tuberculosis immunodiagnosis. In The Gambia, 30% of community controls produced gamma interferon (IFN-γ) in response to ESAT-6. Increased proportions of responders and intensities of responses were found in household contacts. Responses that were initially low in tuberculosis patients increased after treatment. An ESAT-6 IFN-γ assay will be of limited use in the diagnosis of tuberculosis in countries where tuberculosis is endemic. Its role in contact tracing should be evaluated further.