bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct CD4+-T-Cell Responses to Live and Heat-InactivatedAspergillus fumigatusConidia
Authors: Rivera Amariliz , Van Epps Heather L. , Hohl Tobias M. , Rizzuto Gabrielle , Pamer Eric G. 
Published: October 2005

ABSTRACTAspergillus fumigatusis an important fungal pathogen that causes invasive pulmonary disease in immunocompromised hosts. Respiratory exposure toA. fumigatusspores also causes allergic bronchopulmonary aspergillosis, a Th2 CD4+-T-cell-mediated disease that accompanies asthma. The microbial factors that influence the differentiation ofA. fumigatus-specific CD4+T lymphocytes into Th1 versus Th2 cells remain incompletely defined. We therefore examined CD4+-T-cell responses of immunologically intact mice to intratracheal challenge with live or heat-inactivatedA. fumigatusspores. Live but not heat-inactivated fungal spores resulted in recruitment of gamma interferon (IFN-γ)-producing, fungus-specific CD4+T cells to lung airways, achievingA. fumigatus-specific frequencies exceeding 5% of total CD4+T cells. While heat-inactivated spores did not induce detectable levels of IFN-γ-producing,A. fumigatus-specific CD4+T cells in the airways, they did prime CD4+T-cell responses in draining lymph nodes that produced greater amounts of interleukin 4 (IL-4) and IL-13 than T cells responding to live conidia. While immunization with live fungal spores induced antibody responses, we found a marked decrease in isotype-switched,A. fumigatus-specific antibodies in sera of mice following immunization with heat-inactivated spores. Our studies demonstrate that robust Th1 T-cell and humoral responses are restricted to challenge with fungal spores that have the potential to germinate and cause invasive infection. How the adaptive immune system distinguishes between metabolically active and inactive fungal spores remains an important question.
Merozoite Surface Antigen 2 Proteins of
Babesia bovis
Vaccine Breakthrough Isolates Contain a Unique Hypervariable Region Composed of Degenerate Repeats
Authors: Berens Shawn J. , Brayton Kelly A. , Molloy John B. , Bock Russell E. , Lew Ala E. , McElwain Terry F. 
Published: October 2005

ABSTRACT

The merozoite surface antigen 2 (MSA-2) proteins of
Babesia bovis
are members of the variable merozoite surface antigen (VMSA) family that have been implicated in erythrocyte invasion and are important targets for antibody-mediated blocking of invasion. Extensive sequence variation in another VMSA member, MSA-1, has been shown in all vaccine breakthrough isolates. To test the hypothesis that the
msa-2
genes of vaccine breakthrough isolates would also encode a diverse set of proteins, the complete
msa-2
locus was characterized from 12 Australian
B. bovis
strains and isolates, including two vaccine strains and eight vaccine breakthrough isolates, and compared to the loci in previously and newly characterized American strains. In contrast to American strains, the
msa-2
loci of all Australian strains and isolates examined contain, in addition to
msa-2c
, only a solitary gene (designated
msa-2a/b
) closely related to American strain
msa-2a
and
msa-2b
. Nevertheless, the proteins encoded by these genes are quite diverse both between and within geographic regions and harbor evidence of genetic exchange among other VMSA family members, including
msa-1
. Moreover, all but one of the Australian breakthrough isolate MSA-2a/b proteins is markedly different from the vaccine strain from which immune escape occurred, consistent with their role in strain-specific protective immunity. The densest distribution of polymorphisms occurs in a hypervariable region (HVR) within the carboxy third of the molecule that is highly proline rich. Variation in length and content of the HVR is primarily attributable to differences in the order and number of degenerate nucleotide repeats encoding three motifs of unknown function.
Hemagglutinin B Is Involved in the Adherence of
Porphyromonas gingivalis
to Human Coronary Artery Endothelial Cells
Authors: Song Hong , Bélanger Myriam , Whitlock Joan , Kozarov Emil , Progulske-Fox Ann 
Published: October 2005

ABSTRACT

Porphyromonas gingivalis
is a periodontopathogen that may play a role in cardiovascular diseases. Hemagglutinins may function as adhesins and are required for virulence of several bacterial pathogens. The aim of this study was to determine the role of hemagglutinin B (HagB) in adherence of
P. gingivalis
to human coronary artery endothelial (HCAE) cells.
P. gingivalis
strain 381, a
P. gingivalis
381 HagB mutant,
Escherichia coli
JM109 expressing HagB (
E. coli
-HagB), and
E. coli
JM109 containing pUC9 (
E. coli
-pUC9) were tested for their ability to attach to HCAE cells. Inhibition assays were performed to determine the ability of purified recombinant HagB (rHagB) as well as antibodies to HagB, including the polyclonal antibody (PAb) A7985 and the monoclonal antibody (MAb) HL1858, to inhibit the attachment of
P. gingivalis
to HCAE cells. As expected, when the attachment of
P. gingivalis
and the HagB mutant were compared, no statistical significance was observed between the two groups (
P
= 0.331), likely due to the expression of the
hagB
homolog
hagC
. However,
E. coli-
HagB adhered significantly better to HCAE cells than did
E. coli-
pUC9, the control strain. In a competition assay, the presence of purified rHagB decreased bacterial adhesion of
P. gingivalis
or
E. coli-
HagB to HCAE cells. The presence of PAb A7985 or MAb HL1858 also significantly decreased attachment of
P. gingivalis
and
E. coli-
HagB to host cells. These results indicate that HagB is involved in the adherence of
P. gingivalis
to human primary endothelial cells.
Cell-Mediated Protection against PulmonaryYersinia pestisInfection
Authors: Parent Michelle A. , Berggren Kiera N. , Kummer Lawrence W. , Wilhelm Lindsey B. , Szaba Frank M. , Mullarky Isis K. , Smiley Stephen T. 
Published: October 2005

ABSTRACTPulmonary infection with the bacteriumYersinia pestiscauses pneumonic plague, an often-fatal disease for which no vaccine is presently available. Antibody-mediated humoral immunity can protect mice against pulmonaryY. pestisinfection, an experimental model of pneumonic plague. Little is known about the protective efficacy of cellular immunity. We investigated the cellular immune response toY. pestisin B-cell-deficient μMT mice, which lack the capacity to generate antibody responses. To effectively prime pulmonary cellular immunity, we intranasally vaccinated μMT mice with live replicatingY. pestis. Vaccination dramatically increased survival of μMT mice challenged intranasally with a lethalY. pestisdose and significantly reduced bacterial growth in pulmonary, splenic, and hepatic tissues. Vaccination also increased numbers of pulmonary T cells, and administration of T-cell-depleting monoclonal antibodies at the time of challenge abrogated vaccine-induced survival. Moreover, the transfer ofY. pestis-primed T cells to naive μMT mice protected against lethal intranasal challenge. These findings establish that vaccine-primed cellular immunity can protect against pulmonaryY. pestisinfection and suggest that vaccines promoting both humoral and cellular immunity will most effectively combat pneumonic plague.
Blood Group, Immunity, and Risk of Infection withVibrio choleraein an Area of Endemicity
Authors: Harris Jason B. , Khan Ashraful I. , LaRocque Regina C. , Dorer David J. , Chowdhury Fahima , Faruque Abu S. G. , Sack David A. , Ryan Edward T. , Qadri Firdausi , Calderwood Stephen B. 
Published: October 2005

ABSTRACTIndividuals with blood group O are more susceptible than other individuals to severe cholera, although the mechanism underlying this association is unknown. To assess the respective roles of both intrinsic host factors and adaptive immune responses that might influence susceptibility to infection withVibrio cholerae, we prospectively followed a cohort of household contacts of patients with cholera in Bangladesh. In this study, we made the novel observation that persons with blood group O were less likely than those with other blood groups to become infected withV. choleraeO1 (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53 to 0.85;P= 0.008). Consistent with prior studies, however, household contacts with blood group O were more likely to develop severe illness if infected withV. choleraeO1 (OR, 2.3; 95% CI, 0.98 to 5.59;P= 0.05). While blood group O protected significantly against infection withV. choleraeO1, there was no evidence of protection againstV. choleraeO139. A multivariate analysis demonstrated that the association between blood group O and protection from infection withV. choleraeO1 was independent of age, gender, and baseline anti-cholera toxin and vibriocidal antibody titers. Based on this epidemiologic evidence, we propose a hypothesis for understanding the association between blood group O and the risk of infection withV. choleraeO1 and O139 as well as the risk of developing severe symptoms once infected.
CD28 Is Required for Optimal Induction, but Not Maintenance, of Vaccine-Induced Immunity toBlastomyces dermatitidis
Authors: Wüthrich Marcel , Warner Tom , Klein Bruce S. 
Published: October 2005

ABSTRACTCellular immunity mediated by T lymphocytes, in particular CD4+and CD8+type 1 cells, is the main defense against pathogenic fungi. Here, CD28-deficient (CD28−/−) mice were used to study the role of costimulation for the generation and maintenance of T-cell-mediated, type 1 cytokine-dependent mechanisms of vaccine immunity toBlastomyces dermatitidisinfection. Disruption of CD28 costimulation reduced the number of type 1 CD4 and CD8 cells generated and impaired resistance to infection. Type 1 T-cell subsets generated in vaccinated CD28−/−mice were durable and protected mice for at least 3 months after vaccination. Our findings suggest that CD28 is required for the induction of optimal, protective T-cell responses toB. dermatitidisinfection but may be dispensable for the maintenance of T-cell memory.
Loss of Complement Activation and Leukocyte Adherence asNippostrongylus brasiliensisDevelops within the Murine Host
Authors: Giacomin Paul R. , Wang Hui , Gordon David L. , Botto Marina , Dent Lindsay A. 
Published: October 2005

ABSTRACTComplement activation and C3 deposition on the surface of parasitic helminths may be important for recruitment of leukocytes and for damage to the target organism via cell-mediated mechanisms. Inhibition of complement activation would therefore be advantageous to parasites, minimizing damage and enhancing migration through tissues. The aim of this study was to determine ex vivo if complement activation by, and leukocyte adherence to, the nematodeNippostrongylus brasiliensischange as the parasite matures and migrates through the murine host. Pathways of activation of complement and the mechanism of adherence of leukocytes were also defined using sera from mice genetically deficient in either C1q, factor B, C1q and factor B, C3, or C4. Substantive deposition of C3 and adherence of eosinophil-rich leukocytes were seen with infective-stage (L3) but not with lung-stage (L4) larvae. Adult intestinal worms had low to intermediate levels of both C3 and leukocyte binding. For L3 and adult worms, complement deposition was principally dependent on the alternative pathway. For lung-stage larvae, the small amount of C3 detected was dependent to similar degrees on both the lectin and alternative pathways. The classical pathway was not involved for any of the life stages of the parasite. These results suggest that in primary infections, the infective stage ofN. brasiliensisis vulnerable to complement-dependent attack by leukocytes. However, within the first 24 h of infection,N. brasiliensisacquires the ability to largely avoid complement-dependent immune responses.
Differential Cytokine Production and Toll-Like Receptor Signaling Pathways by
Candida albicans
Blastoconidia and Hyphae
Authors: van der Graaf Chantal A. A. , Netea Mihai G. , Verschueren Ineke , van der Meer Jos W. M. , Kullberg Bart Jan 
Published: October 2005

ABSTRACT

Toll-like receptors (TLR) are crucial for an efficient antifungal defense. We investigated the differential recognition of blastoconidia and hyphae of
Candida albicans
by TLRs. In contrast to
Candida
blastoconidia, which stimulated large amounts of gamma interferon (IFN-γ), the tissue-invasive
Candida
hyphae did not stimulate any IFN-γ by human peripheral blood mononuclear cells (PBMC) or murine splenic lymphocytes. After stimulation with blastoconidia, the production of IFN-γ was TLR4 dependent, as shown by the significantly decreased IFN-γ production in anti-TLR4-treated PBMC and in splenic lymphocytes from TLR4-defective ScCr mice. In addition, peritoneal macrophages from ScCr mice produced less tumor necrosis factor α (TNF-α) than macrophages of control mice did when stimulated with
Candida
blastoconidia, but not with hyphae, indicating that TLR4-mediated signals are lost during hyphal germination. In contrast, macrophages from TLR2 knockout mice had a decreased production of TNF-α in response to both
Candida
blastoconidia and hyphae.
Candida
hyphae stimulated production of interleukin-10 through TLR2-dependent mechanisms. In conclusion, TLR4 mediates proinflammatory cytokine induction after
Candida
stimulation, whereas
Candida
recognition by TLR2 leads mainly to anti-inflammatory cytokine release. TLR4-mediated proinflammatory signals are lost during germination of
Candida
blastoconidia into hyphae. Phenotypic switching during germination may be an important escape mechanism of
C. albicans
, resulting in counteracting host defense.
MyD88-Dependent Signaling Contributes to Protection following
Bacillus anthracis
Spore Challenge of Mice: Implications for Toll-Like Receptor Signaling
Authors: Hughes Molly A. , Green Candace S. , Lowchyj Lisa , Lee Gloria M. , Grippe Vanessa K. , Smith Michael F. , Huang Li-Yun , Harvill Eric T. , Merkel Tod J. 
Published: October 2005

ABSTRACT

Bacillus anthracis
is a spore-forming, gram-positive organism that is the causative agent of the disease anthrax. Recognition of
Bacillus anthracis
by the host innate immune system likely plays a key protective role following infection. In the present study, we examined the role of TLR2, TLR4, and MyD88 in the response to
B. anthracis.
Heat-killed
Bacillus anthracis
stimulated TLR2, but not TLR4, signaling in HEK293 cells and stimulated tumor necrosis factor alpha (TNF-α) production in C3H/HeN, C3H/HeJ, and C57BL/6J bone marrow-derived macrophages. The ability of heat-killed
B. anthracis
to induce a TNF-α response was preserved in TLR2
−/−
but not in MyD88
−/−
macrophages. In vivo studies revealed that TLR2
−/−
mice and TLR4-deficient mice were resistant to challenge with aerosolized Sterne strain spores but MyD88
−/−
mice were as susceptible as A/J mice. We conclude that, although recognition of
B. anthracis
occurs via TLR2, additional MyD88-dependent pathways contribute to the host innate immune response to anthrax infection.
Comparison of Immune Responses to Gonococcal PorB Delivered as Outer Membrane Vesicles, Recombinant Protein, or Venezuelan Equine Encephalitis Virus Replicon Particles
Authors: Zhu Weiyan , Thomas Christopher E. , Chen Ching-ju , Van Dam Cornelius N. , Johnston Robert E. , Davis Nancy L. , Sparling P. Frederick 
Published: October 2005

ABSTRACTPorin (PorB) is a major outer membrane protein produced by allNeisseria gonorrhoeaestrains and has been a focus of intense interest as a vaccine candidate. In this study, the immunogenicity of PorB in mice was investigated after several immunization regimens. Outer membrane vesicles (OMV), recombinant renatured PorB (rrPorB), and PorB-expressing Venezuelan equine encephalitis (VEE) virus replicon particles (PorB VRP) were delivered intranasally (i.n.) or subcutaneously (s.c.) into the dorsal area or the hind footpad in three-dose schedules; the PorB VRP-immunized mice were given a single additional booster dose of rrPorB in Ribi adjuvant. Different delivery systems and administration routes induced different immune responses. Mice immunized s.c. with rrPorB in Ribi had the highest levels of PorB-specific serum immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. Surprisingly, there was an apparent Th1 bias, based on IgG1/IgG2a ratios, after immunization with rrPorB in Ribi in the footpad while the same vaccine given in the dorsal area gave a strongly Th2-biased response. PorB VRP-immunized mice produced a consistent Th1 response with a high gamma interferon response in stimulated splenic lymphocytes and very low IgG1/IgG2a ratios. Immunization by OMV delivered i.n. was the only regimen that resulted in a serum bactericidal response, and it generated an excellent mucosal IgA response. Serum from mice immunized with rrPorB preferentially recognized the surface of whole gonococci expressing a homologous PorB, whereas serum from PorB VRP-immunized mice had relatively low whole-cell binding activity but recognized both heterologous and homologous PorB equally. The data resulting from this direct comparison suggested that important aspects of the immune response can be manipulated by altering the form of the antigen and its delivery. This information coupled with an understanding of protective antigonococcal immune responses will enable the design of the optimal vaccine forN. gonorrhoeae.
Additive Effect on Intracellular Growth byLegionella pneumophilaIcm/Dot Proteins Containing a Lipobox Motif
Authors: Yerushalmi Gal , Zusman Tal , Segal Gil 
Published: October 2005

ABSTRACTLegionella pneumophila, the causative agent of Legionnaires' disease, utilizes a type IVB secretion system to subvert its host cells and grow intracellularly. This type IV secretion system is composed of 25icm(ordot) genes that probably constitute parts of a secretion complex as well as more than 30 proteins that are translocated via this system into the host cells. Three of the Icm/Dot proteins (DotD, DotC, and IcmN) contain a lipobox motif at their N terminals and are predicted to be lipoproteins. Two of these lipoproteins (DotD and DotC) were found to be essential for intracellular growth in both HL-60-derived human macrophages and in the protozoan hostAcanthamoeba castellanii, while the third lipoprotein (IcmN) was found to be partially required for intracellular growth only inA. castellanii. Mutation analysis of the lipobox cysteine residue, which was shown previously to be indispensable for the lipobox function, indicated that both DotC and DotD are partially functional without this conserved residue. Cysteine mutations in both DotC and DotD or in DotC together with anicmNdeletion or in DotD together with anicmNdeletion were found to be additive, indicating that each of these lipoproteins performs its function independently from the others. Analysis of the transcriptional regulation of both thedotDCoperon and theicmNgene revealed that both had higher levels of expression at stationary phase which were partially dependent on the LetA regulator. Our results indicate that the lipoproteins of theL. pneumophila icm(ordot) system are essential components of the secretion system and that they perform their functions independently.
Variations inHelicobacter pyloriLipopolysaccharide To Evade the Innate Immune Component Surfactant Protein D
Authors: Khamri Wafa , Moran Anthony P. , Worku Mulugeta L. , Karim Q. Najma , Walker Marjorie M. , Annuk Heidi , Ferris John A. , Appelmelk Ben J. , Eggleton Paul , Reid Kenneth B. M. , Thursz Mark R. 
Published: October 2005

ABSTRACTHelicobacter pyloriis a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregatingH. pylori. Wide variation in the SP-D binding affinity toH. pylorihas been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show thatH. pylorievades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P= 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen.
Vaginal Epithelial Cell Anti-
Candida albicans
Activity Is Associated with Protection against Symptomatic Vaginal Candidiasis
Authors: Barousse Melissa M. , Espinosa Terri , Dunlap Kathleen , Fidel Paul L. 
Published: October 2005

ABSTRACT

Vaginal epithelial cell (VEC) anti-
Candida albicans
activity, despite being measured in vitro, is considered an innate host defense mechanism. This was supported further by the fact that women protected from symptomatic infection following a live intravaginal
Candida
challenge had increased VEC anti-
Candida
activity compared to those who acquired a symptomatic infection.
Detecting altered postural control after cerebral concussion in athletes with normal postural stability
Authors: Cavanaugh J T , Guskiewicz K M , Giuliani C , Marshall S , Mercer V , Stergiou N 
Published: October 2005

Objective:To determine if approximate entropy (ApEn), a regularity statistic from non-linear dynamics, could detect changes in postural control during quiet standing in athletes with normal postural stability after cerebral concussion.Methods:The study was a retrospective, case series analysis of centre of pressure (COP) data collected during the Sensory Organization Test (SOT) from NCAA Division I (USA) athletes prior to and within 48 h after injury. Subjects were 21 male and six female athletes from a variety of sports who sustained a cerebral concussion between 1997 and 2003. After injury, athletes displayed normal postural stability equivalent to preseason levels. For comparison, COP data also were collected from 15 male and 15 female healthy non-athletes on two occasions. ApEn values were calculated for COP anterior-posterior (AP) and medial-lateral (ML) time series.Results:Compared to healthy subjects, COP oscillations among athletes generally became more regular (lower ApEn value) after injury despite the absence of postural instability. For AP time series, declines in ApEn values were much larger in SOT conditions 1 and 2 (approximately three times as large as the standard error of the mean) than for all other conditions. For ML time series, ApEn values declined after injury in all sensory conditions (F1,55 = 6.36, p = 0.02).Conclusions:Athletes who demonstrated normal postural stability after concussion nonetheless displayed subtle changes in postural control. Changes in ApEn may have represented a clinically abnormal finding. ApEn analysis of COP oscillations may be a valuable supplement to existing concussion assessment protocols for athletes.