bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Host Resistance to Primary and SecondaryListeria monocytogenesInfections in Mice by Intranasal and Intravenous Routes
Authors: Mizuki Mayuko , Nakane Akio , Sekikawa Kenji , Tagawa Yoh-ich , Iwakura Yoichiro 
Published: October 2002

ABSTRACTThere have been no studies on the susceptibility and host immune responses to an intranasal infection withListeria monocytogenes. In this study, we compared the susceptibilities and cytokine responses between intranasal and intravenous infections withL. monocytogenesin mice. Moreover, we compared efficiency of acquisition of host resistance toL. monocytogenesinfection between intranasally and intravenously immunized mice because an intranasal immunization of vaccines is reportedly available for induction of adaptive immunity against various infectious pathogens. The susceptibility to an intranasal infection withL. monocytogeneswas markedly lower than that to the intravenous infection. The bacterial growth in the lungs, spleens, and livers was substantially similar between intranasally and intravenously infected mice. Titers of endogenous gamma interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) in the spleens, livers, and lungs were parallel to bacterial numbers in each organ of mice during intranasal infection and intravenous infection. IFN-γ-deficient mice and TNF-α-deficient mice were highly susceptible to intranasal infection as well as intravenous infection. Susceptibilities to intranasal and intravenousL. monocytogenesinfection were the same in these cytokine-deficient mice. These results suggest that both IFN-γ and TNF-α play critical roles in host resistance to intranasalL. monocytogenesinfection as well as the intravenous infection. Acquisition of host resistance to intravenous and intranasalL. monocytogenesinfection was induced in intranasally immunized mice as well as intravenously immunized mice, suggesting that intranasal immunization is effective for prevention of a systemic infection withL. monocytogenes.
Macrophage Plasma Membrane Cholesterol Contributes to
Brucella abortus
Infection of Mice
Authors: Watarai Masahisa , Makino Sou-ichi , Michikawa Makoto , Yanagisawa Katsuhiko , Murakami Shigeru , Shirahata Toshikazu 
Published: October 2002

ABSTRACT

Brucella abortus
is a facultative intracellular bacterium capable of surviving inside macrophages. Intracellular replication of
B. abortus
requires the VirB complex, which is highly similar to conjugative DNA transfer systems. In this study, we show that plasma membrane cholesterol of macrophages is required for the VirB-dependent internalization of
B. abortus
and also contributes to the establishment of bacterial infection in mice. The internalization of
B. abortus
was accelerated by treating macrophages with acetylated low-density lipoprotein (acLDL). Treatment of acyl coenzyme A:cholesterol acyltransferase inhibitor, HL-004, to macrophages preloaded with acLDL accelerated the internalization of
B. abortus
. Ketoconazole, which inhibits cholesterol transport from lysosomes to the cell surface, inhibited the internalization and intracellular replication of
B. abortus
in macrophages. The Niemann-Pick C1 gene (NPC1), the gene for Niemann-Pick type C disease, characterized by an accumulation of cholesterol in most tissues, promoted
B. abortus
infection. NPC1-deficient mice were resistant to the bacterial infection. Molecules associated with cholesterol-rich microdomains, “lipid rafts,” accumulate in intracellular vesicles of macrophages isolated from NPC1-deficient mice, and the macrophages yielded no intracellular replication of
B. abortus
. Thus, trafficking of cholesterol-associated microdomains controlled by NPC1 is critical for the establishment of
B. abortus
infection.
Incorporation ofN-Acetylneuraminic Acid intoHaemophilus somnusLipooligosaccharide (LOS): Enhancement of Resistance to Serum and Reduction of LOS Antibody Binding
Authors: Inzana Thomas J. , Glindemann Gretchen , Cox Andrew D. , Wakarchuk Warren , Howard Michael D. 
Published: October 2002

ABSTRACTHaemophilus somnusisolates from cases of thrombotic meningoencephalitis, pneumonia, and other disease sites are capable of undergoing a high rate of phase variation in the oligosaccharide component of their lipooligosaccharides (LOS). In contrast, the LOS of commensal strains isolated from the normal reproductive tract phase vary little or not at all. In addition, the LOS ofH. somnusshares conserved epitopes with LOS fromNeisseria gonorrhoeae,Haemophilus influenzae, and other species that can incorporate sialic acid into their LOS. We now report that growth of disease isolates ofH. somnuswith CMP-N-acetylneuraminic acid (CMP-NeuAc) or NeuAc added to the medium resulted in incorporation of NeuAc into the LOS. However, NeuAc was not incorporated into the LOS of commensal isolates and one disease isolate following growth in medium containing CMP-NeuAc or NeuAc. Sialylated LOS was detected by an increase in the molecular size or an increase in the amount of the largest-molecular-size LOS electrophoretic bands, which disappeared following treatment with neuraminidase. Sialylated LOS could also be detected by reactivity withLimax flavusagglutinin lectin, which is specific for sialylated species, by dot blot assay; this reactivity was also reversed by neuraminidase treatment.H. somnusstrain 2336 LOS was found to contain some sialic acid when grown in medium lacking CMP-NeuAc or NeuAc, although supplementation enhanced NeuAc incorporation. In contrast strain 738, an LOS phase variant of strain 2336, was less extensively sialylated when the growth medium was supplemented with CMP-NeuAc or NeuAc, as determined by electrophoretic profiles and electrospray mass spectrometry. The sialyltransferase ofH. somnusstrain 738 was confirmed to preferentially sialylate the Galβ-(1-3)-GlcNAc component of the lacto-N-tetraose structure by capillary electrophoresis assay. Enhanced sialylation of the strain 2336 LOS inhibited the binding of monoclonal antibodies to LOS by enzyme immunoassay and Western blotting. Furthermore, sialylation of the LOS enhanced the resistance ofH. somnusto the bactericidal action of antiserum to LOS. Sialylation and increased resistance to killing by normal serum also occurred in a deletion mutant that was deficient in the terminal Gal-GlcNAc disaccharide. LOS sialylation may therefore be an important virulence mechanism to protectH. somnusagainst the host immune system.
Protection from Group B Streptococcal Infection in Neonatal Mice by Maternal Immunization with Recombinant Sip Protein
Authors: Martin Denis , Rioux Stéphane , Gagnon Edith , Boyer Martine , Hamel Josée , Charland Nathalie , Brodeur Bernard R. 
Published: October 2002

ABSTRACT
The protective potential of antibodies directed against group B streptococcus (GBS) Sip surface protein was determined by using the mouse neonatal infection model. Rabbit Sip-specific antibodies administered passively to pregnant mice protected their pups against a GBS lethal challenge. In addition, active immunization with purified recombinant Sip protein of female CD-1 mice induced the production of specific antibodies that also confer protection to the newborn pups against GBS strains of serotypes Ia/c, Ib, II, III, and V. These data confirm that Sip-specific antibodies can cross the placenta and conferred protective immunity against GBS infections.
The
Haemophilus influenzae
Hap Autotransporter Binds to Fibronectin, Laminin, and Collagen IV
Authors: Fink Doran L. , Green Bruce A. , St. Geme Joseph W. 
Published: October 2002

ABSTRACT

Nontypeable
Haemophilus influenzae
(NTHI) initiates infection by colonizing the upper respiratory tract mucosa. NTHI disease frequently occurs in the context of respiratory tract inflammation, where organisms encounter damaged epithelium and exposed basement membrane. In this study, we examined interactions between the
H. influenzae
Hap adhesin and selected extracellular matrix proteins. Hap is an autotransporter protein that undergoes autoproteolytic cleavage, with release of the adhesive passenger domain, Hap
s
, from the bacterial cell surface. We found that Hap promotes bacterial adherence to purified fibronectin, laminin, and collagen IV and that Hap-mediated adherence is enhanced by inhibition of autoproteolysis. Adherence is inhibited by pretreatment of bacteria with a polyclonal antiserum recognizing Hap
s
. Purified Hap
s
binds with high affinity to fibronectin, laminin, and collagen IV but not to collagen II. Binding of Hap
s
to fibronectin involves interaction with the 45-kDa gelatin-binding domain but not the 30-kDa heparin-binding domain of fibronectin. Taken together, these observations suggest that interactions between Hap and extracellular matrix proteins may play an important role in NTHI colonization of the respiratory tract.
Prevalence and Boosting of Antibodies toPlasmodium falciparumGlycosylphosphatidylinositols and Evaluation of Their Association with Protection from Mild and Severe Clinical Malaria
Authors: de Souza J. Brian , Todd James , Krishegowda Gowdahalli , Gowda D. Channe , Kwiatkowski Dominic , Riley Eleanor M. 
Published: October 2002

ABSTRACTGlycosylphosphatidylinositols (GPIs), the anchor molecules of some membrane proteins ofPlasmodiumspecies, have been implicated in the induction of immunopathology during malaria infections. Hence, neutralization of GPIs by antibodies may reduce the severity of clinical attacks of malaria. To test this hypothesis, we have assessed the levels of anti-GPI antibodies in plasma from children and adults living in areas of seasonal malaria transmission in The Gambia. In a prospective study of susceptibility to clinical or asymptomatic infection, the levels of anti-GPI antibodies were measured before and after the transmission season. Samples were also obtained from children recruited into a hospital-based study of severe malaria. We find that in malaria-exposed individuals both the prevalence and the concentration of anti-GPI antibodies increase with age and that antibody levels are significantly higher at the end of the malaria transmission season than at the start of the season. Antibody levels are also higher in children with asymptomatic infections (i.e., those with a degree of clinical immunity) than in children who developed clinical malaria and high parasitemia, although this difference is not statistically significant. Importantly, antibodies appear to be rapidly boosted by clinical malaria infection, but children under the age of two years are seronegative for anti-GPI antibodies, even during an acute infection. While GPIs may be involved in the pathogenesis of human malaria, the data from this study do not provide any strong evidence to support the notion that anti-GPI antibodies confer resistance to mild or severe malarial disease. Further case-control studies, ideally of a prospective nature, are required to elucidate the role of antiglycolipid antibodies in protection from severe malaria.
Antibodies toPlasmodium falciparumGlycosylphosphatidylinositols: Inverse Association with Tolerance of Parasitemia in Papua New Guinean Children and Adults
Authors: Boutlis Craig S. , Gowda D. Channe , Naik Ramachandra S. , Maguire Graeme P. , Mgone Charles S. , Bockarie Moses J. , Lagog Moses , Ibam Erwin , Lorry Kerry , Anstey Nicholas M. 
Published: October 2002

ABSTRACTIndividuals living in regions of intense malaria transmission exhibit natural immunity that facilitates persistence of parasitemia at controlled densities for much of the time without symptoms. This aspect of immunity has been referred to as malarial “tolerance” and is thought to partly involve inhibition of the chain of events initiated by a parasite toxin(s) that may otherwise result in cytokine release and symptoms such as fever. Antibodies to the candidatePlasmodium falciparumglycosylphosphatidylinositol (GPI) toxin have been viewed as likely mediators of such tolerance. In this study, the relationship between antibodies toP. falciparumGPIs, age, and parasitemia was determined in asymptomatic children and adults living in Madang, Papua New Guinea. The prevalence and intensity of antibody responses increased with age and were lowest in children 1 to 4 years old with the highest-density parasitemias. In children of this age group who were tolerant of parasitemia during the study, only 8.3% had detectable immunoglobulin G (IgG) and none had IgM antibodies to GPI. This suggests that anti-GPI antibodies are unlikely to be the sole mediator of malarial tolerance, especially in children younger than 5 years. Following antimalarial treatment, clearance of parasitemia led to a fall in anti-GPI IgG response in children and adolescents within 6 weeks. As anti-GPI antibodies potentially play a role in protecting against disease progression, our results caution against the treatment of asymptomatic parasitemia and suggest that generation of a sustained antibody response in children poses a challenge to novel antitoxic vaccination strategies.
Endogenous Interleukin-12 Is Critical for Controlling the Late but Not the Early Stage ofLeishmania mexicanaInfection in C57BL/6 Mice
Authors: Aguilar Torrentera Fabiola , Laman Jon D. , Van Meurs Marjan , Adorini Luciano , Muraille Eric , Carlier Y. 
Published: October 2002

ABSTRACTThe role of interleukin-12 (IL-12) has been clearly established in the resistance of C57BL/6 (B6) mice toLeishmania majorinfection, but its involvement in the control ofLeishmania mexicanainfection remains to be determined. Here, we show the following. (i)L. mexicana, in contrast toL. major, induces the development of nonhealing lesions in B6 mice. (ii) Cells expressing IL-12p40, gamma interferon (IFN-γ), NOS2, and CD40L are numerous in the footpad lesion and/or the draining popliteal lymph node of animals infected for up to 14 weeks withL. mexicana. (iii) B6 mice, either IL-12p40 deficient or treated with IL-12p40-neutralizing antibodies, display a dramatic enhancement of primary and secondary lesions leading to death 10 weeks after inoculation withL. mexicana. (iv) Splenocytes harvested 4 and 8 weeks after infection of IL-12p40−/−B6 mice withL. mexicanaare unable to produce IFN-γ, but secrete IL-4, IL-10, and IL-18. Thus, the early control ofL. mexicanainfection by B6 mice is independent of IL-12, whereas IL-12 and Th1 responses play a key role in controlling the late stages ofL. mexicanainfection. However, they fail to resolve lesions, in contrast toL. majorinfection, emphasizing the different outcomes induced by these twoLeishmaniaspecies in B6 mice.
Ganglioside Mimicry ofCampylobacter jejuniLipopolysaccharides Determines Antiganglioside Specificity in Rabbits
Authors: Ang C. W. , Noordzij P. G. , de Klerk M. A. , Endtz H. P. , van Doorn P. A. , Laman J. D. 
Published: October 2002

ABSTRACTThe core oligosaccharides ofCampylobacter jejunilipopolysaccharides (LPS) display molecular mimicry with gangliosides. Cross-reactive anti-LPS-antiganglioside antibodies have been implicated to show a crucial role in the pathogenesis of the Guillain-Barré and Miller Fisher syndrome. The specificity of the antiganglioside response is thought to depend on the oligosaccharide structure of the ganglioside mimic. To test this hypothesis and to investigate the potential of LPS fromCampylobacterstrains from enteritis patients to induce an antiganglioside response, we immunized rabbits with purified LPS from eightCampylobacter jejunireference strains with biochemically well-defined distinct ganglioside mimics and determined the presence of antiganglioside antibodies. All rabbits produced immunoglobulin G (IgM) and IgG anti-LPS antibodies, and the specificity of the cross-reactive antiganglioside response indeed corresponded with the biochemically defined mimic. Most rabbits also had antibody reactivity against additional gangliosides, and there were slight differences in the fine specificity of the antibody response between rabbits that had been immunized with LPS from the sameCampylobacterstrain. High anti-LPS and antiganglioside titers persisted over a 10-month period. In conclusion, the structure of the LPS only partly determines the antiganglioside specificity. Other strain-specific as well as host-related factors influence the induction and fine-specificity of the cross-reactive anti-LPS-antiganglioside response.
Fcγ Receptor I- and III-Mediated Macrophage Inflammatory Protein 1α Induction in Primary Human and Murine Microglia
Authors: Song Xianyuan , Shapiro Scott , Goldman David L. , Casadevall Arturo , Scharff Matthew , Lee Sunhee C. 
Published: October 2002

ABSTRACTMicroglial cell phagocytic receptors may play important roles in the pathogenesis and treatment of several neurological diseases. We studied microglial Fc receptor (FcR) activation with respect to the specific FcγR types involved and the downstream signaling events by using monoclonal antibody (MAb)-coatedCryptococcus neoformansimmune complexes as the stimuli and macrophage inflammatory protein 1α (MIP-1α) production as the final outcome.C. neoformanscomplexed with murine immunoglobulin G (IgG) of γ1, γ2a, and γ3, but not γ2b isotype, was effective in inducing MIP-1α in human microglia. Since murine γ2b binds to human FcγRII (but not FcγRI or FcγRIII), these results indicate that FcγRI and/or FcγRIII is involved in MIP-1α production. Consistent with this, an antibody that blocks FcγRII (IV.3) failed to inhibit MIP-1α production, while an antibody that blocks FcγRIII (3G8) did. An anti-C. neoformansMAb, 18B7 (IgG1), but not its F(ab′)2, induced extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase kinase phosphorylation, and MIP-1α release was suppressed by the ERK inhibitor U0126.C. neoformansplus 18B7 also induced degradation of I-κBα, and MIP-1α release was suppressed by the antioxidant NF-κB inhibitor pyrrolidine dithiocarbamate. To confirm the role of FcR more directly, we isolated microglia from wild-type and various FcR-deficient mice and then challenged them withC. neoformansplus 18B7. While FcγRII-deficient microglia showed little difference from the wild-type microglia, both FcγRI α-chain- and FcγRIII α-chain-deficient microglia produced less MIP-1α, and the common Fc γ-chain-deficient microglia showed no MIP-1α release. Taken together, our results demonstrate a definitive role for FcγRI and FcγRIII in microglial chemokine induction and implicate ERK and NF-κB as the signaling components leading to MIP-1α expression. Our results delineate a new mechanism for microglial activation and may have implications for central nervous system inflammatory diseases.
Mechanism of Entry Determines the Ability ofToxoplasma gondiiTo Inhibit Macrophage Proinflammatory Cytokine Production
Authors: Butcher Barbara A. , Denkers Eric Y. 
Published: October 2002

ABSTRACTMacrophages (Mφ) infected with tachyzoites of the opportunistic protozoanToxoplasma gondiiare blocked in production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-12 (IL-12) in response to lipopolysaccharide (LPS) triggering, and this is associated with parasite-induced inhibition of NFκB translocation. Here, we demonstrate a requirement for active invasion in the ability of the parasite to mediate suppression. Neither soluble tachyzoite antigen nor secreted products were suppressive, and heat-inactivated, antibody-coated tachyzoites, which efficiently entered the cell through receptor-mediated uptake, failed to inhibit LPS responses. Cytochalasin D, a drug blocking tachyzoite invasion of, but not adherence to, Mφ, severely curtailedToxoplasma-induced suppression. In addition, parasite-induced nonresponsiveness, as measured by TNF-α production, was reversed by treating infected cells with the toxoplasmastatic drugs pyrimethamine and 6-thioxanthine prior to LPS stimulation. A divergence in IL-12 and TNF-α responses was found during extended incubation of tachyzoites and Mφ in that 24 h of incubation of infected Mφ resulted in IL-12, but not TNF-α, secretion, and production of the latter cytokine remained suppressed when these cells were subjected to LPS triggering. Our results demonstrate that active invasion and survival of the parasite within the parasitophorous vacuole are required to induce and maintain Mφ cytokine-specific nonresponsiveness to LPS. They also show that the effects ofToxoplasmaon IL-12 and TNF-α production are nonidentical, with the parasite exerting a longer-lasting suppression of the latter.
Contribution of
Candida albicans ALS1
to the Pathogenesis of Experimental Oropharyngeal Candidiasis
Authors: Kamai Yasuki , Kubota Mikie , Kamai Yoko , Hosokawa Tsunemichi , Fukuoka Takashi , Filler Scott G. 
Published: October 2002

ABSTRACT

We investigated the contribution of
Candida albicans ALS1
, which encodes a candidal adhesin, to the pathogenesis of experimental murine oropharyngeal candidiasis. Our results indicate that the
ALS1
gene product is important for the adherence of the organism to the oral mucosa during the early stage of the infection.
Lipopolysaccharide Desensitization of Macrophages Provides Protection againstYersinia enterocolitica-Induced Apoptosis
Authors: Ruckdeschel Klaus , Richter Kathleen 
Published: October 2002

ABSTRACTPathogenicYersiniaspp. uncouple an array of signal transduction pathways in macrophages to disrupt their response to infection. This compels the macrophage to undergo apoptosis. Our study shows that macrophages that had acquired tolerance toYersiniainfection by preexposure to lipopolysaccharide were considerably protected againstY. enterocolitica-induced apoptosis. The desensitization of macrophages by lipopolysaccharide, which is thought to be a self-protective, adaptive response to sustained bacterial stimulation, may represent an immune mechanism that aids in overcomingYersinia-mediated apoptosis and infection.
A Mutant ofBurkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis
Authors: Atkins T. , Prior R. G. , Mack K. , Russell P. , Nelson M. , Oyston P. C. F. , Dougan G. , Titball R. W. 
Published: October 2002

ABSTRACTUsing a transposon mutagenesis approach, we have identified a mutant ofBurkholderia pseudomalleithat is auxotrophic for branched chain amino acids. The transposon was shown to have interrupted theilvIgene encoding the large subunit of the acetolactate synthase enzyme. Compared to the wild type, this mutant was significantly attenuated in a murine model of disease. Mice inoculated intraperitoneally with the auxotrophic mutant, 35 days prior to challenge, were protected against a challenge dose of 6,000 median lethal doses of wild-typeB. pseudomallei.
Short-Sequence Tandem and Nontandem DNA Repeats and Endogenous Hydrogen Peroxide Production Contribute to Genetic Instability ofStreptococcus pneumoniae
Authors: Pericone Christopher D. , Bae Deborah , Shchepetov Mikhail , McCool Tera , Weiser Jeffrey N. 
Published: October 2002

ABSTRACTLoss-of-function mutations in the following seven pneumococcal genes were detected and analyzed:pspA,spxB,xba,licD2,lytA,nanA, andatpC. Factors associated with these mutations included (i) frameshifts caused by reversible gain and loss of single bases within homopolymeric repeats as short as 6 bases, (ii) deletions caused by recombinational events between nontandem direct repeats as short as 8 bases, and (iii) substitutions of guanine residues caused at an increased frequency by the high levels of hydrogen peroxide (>2 mM) typically generated by this species under aerobic growth conditions. The latter accounted for a frequency as high as 2.8 × 10−6for spontaneous mutation to resistance to optochin and was 10- to 200-fold lower in the absence of detectable levels of H2O2. Some of these mutations appear to have been selected for in vivo during pneumococcal infection, perhaps as a consequence of immune pressure or oxidative stress.