bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Role for B Lymphocytes and CD4
+
T Cells in Immunity to Infection by the Attaching and Effacing Pathogen
Citrobacter rodentium
Authors: Simmons Cameron P. , Clare Simon , Ghaem-Maghami Marjan , Uren Tania K. , Rankin Joanna , Huett Allan , Goldin Rob , Lewis David J. , MacDonald Thomas T. , Strugnell Richard A. , Frankel Gad , Dougan Gordon 
Published: August 2003

ABSTRACT

Citrobacter rodentium
, an attaching-effacing bacterial pathogen, establishes an acute infection of the murine colonic epithelium and induces a mild colitis in immunocompetent mice. This study describes the role of T-cell subsets and B lymphocytes in immunity to
C. rodentium
. C57Bl/6 mice orally infected with
C. rodentium
resolved infection within 3 to 4 weeks. Conversely, systemic and colonic tissues of RAG1
−/−
mice orally infected with
C. rodentium
contained high and sustained pathogen loads, and in the colon this resulted in a severe colitis. C57Bl/6 mice depleted of CD4
+
T cells, but not CD8
+
T cells, were highly susceptible to infection and also developed severe colitis. Mice depleted of CD4
+
T cells also had diminished immunoglobulin G (IgG) and IgA antibody responses to two
C. rodentium
virulence-associated determinants, i.e., EspA and intimin, despite having a massively increased pathogen burden. Mice with an intact T-cell compartment, but lacking B cells (μMT mice), were highly susceptible to
C. rodentium
infection. Systemic immunity, but not mucosal immunity, could be restored by adoptive transfer of convalescent immune sera to infected μMT mice. Adoptive transfer of immune B cells, but not naïve B cells, provided highly variable immunity to recipient μMT mice. The results suggest that B-cell-mediated immune responses are central to resolution of a
C. rodentium
infection but that the mechanism through which this occurs requires further investigation. These data are relevant to understanding immunity to enteric attaching and effacing bacterial pathogens of humans.
Serum Opacity Factor (SOF) ofStreptococcus pyogenesEvokes Antibodies That Opsonize Homologous and Heterologous SOF-Positive Serotypes of Group A Streptococci
Authors: Courtney Harry S. , Hasty David L. , Dale James B. 
Published: August 2003

ABSTRACTSerum opacity factor (SOF) is a protein expressed byStreptococcus pyogenesthat opacifies mammalian serum. SOF is also a virulence factor ofS. pyogenes, but it has not been previously shown to elicit a protective immune response. Herein, we report that SOF evokes bactericidal antibodies againstS. pyogenesin humans, rabbits, and mice. Rabbit antiserum against purified recombinant SOF2 opsonized SOF-positive M type 2, 4, and 28S. pyogenesin human blood but had no effect on SOF-negative M type 5S. pyogenes. Furthermore, affinity-purified human antibodies against SOF2 also opsonized SOF-positive streptococci. A combination of antisera against M2 and SOF2 proteins was dramatically more effective in killing streptococci than either antiserum alone, indicating that antibodies against SOF2 enhance the opsonic efficiency of M protein antibodies. Mice tolerated an intravenous injection of 100 μg of SOF without overt signs of toxicity, and immunization with SOF protected mice against challenge infections with M type 2S. pyogenes. These data indicate that SOF evokes opsonic antibodies that may protect against infections by SOF-positive serotypes of group A streptococci and suggest that different serotypes of SOF have common epitopes that may be useful vaccine candidates to protect against group A streptococcal infections.
Characterization of Antibody Responses to
Wolbachia
Surface Protein in Humans with Lymphatic Filariasis
Authors: Punkosdy George A. , Addiss David G. , Lammie Patrick J. 
Published: August 2003

ABSTRACT

Symbiotic
Wolbachia
organisms of filarial nematodes have received much attention as possible chemotherapy targets and disease-causing organisms. In order to further investigate the association between anti-
Wolbachia
immune responses and chronic filarial disease in humans, antibody responses to
Wolbachia
surface protein (WSP) were assayed in serum samples collected from 232 individuals living in Leogane, Haiti, an area where
Wuchereria bancrofti
infection is endemic, and from 67 North Americans with no history of lymphatic filariasis. As opposed to antifilarial antibody responses, which were largely influenced by the patient's infection status, the prevalence and levels of anti-WSP immunoglobulin G (IgG) antibodies among individuals with lymphedema or hydrocele were significantly greater than those in gender- and infection-matched individuals without disease. In at least one case, the anti-WSP IgG response was coincident with the onset of lymphedema development, and among anti-WSP-positive women with lymphedema, anti-WSP IgG levels were negatively correlated with the duration of lymphedema. The presence of anti-WSP IgG was also associated with the severity of inguinal adenopathy among men with hydrocele. In addition to the presence of anti-WSP antibodies among Haitians, 15 of 67 (22%) serum samples collected from individuals from North America, where filariasis is not endemic, were also positive for anti-WSP antibodies. In comparison to those from Haitians, anti-WSP antibodies from North Americans primarily recognized a distinct region of WSP located within the highly conserved second transmembrane domain. The results of this study demonstrate that anti-WSP antibody responses are associated with the presence of chronic filarial morbidity and not filarial infection status in humans and suggest that WSP should be further studied as a potential trigger for the development of filarial disease.
Coinjection with CpG-Containing Immunostimulatory Oligodeoxynucleotides Reduces the Pathogenicity of a Live Vaccine against Cutaneous Leishmaniasis but Maintains Its Potency and Durability
Authors: Mendez Susana , Tabbara Khaled , Belkaid Yasmine , Bertholet Sylvie , Verthelyi Daniela , Klinman Dennis , Seder Robert A. , Sacks David L. 
Published: August 2003

ABSTRACTThe inoculation of live, nonattenuatedLeishmania majorto produce a lesion in a selected site that heals, referred to as leishmanization, is to date the only vaccine against leishmaniasis that has proven to be effective in humans. Its use has been restricted or abandoned entirely, however, due to safety concerns. In an attempt to develop a leishmanization protocol that minimizes pathology while maintaining long-term protection, live parasites were coinjected with CpG-containing immunostimulatory oligodeoxynucleotides (CpG ODNs) alone or in combination with whole-cell lysates of heat-killedL. majorpromastigotes bound to alum (ALM). C57BL/6 mice infected intradermally by usingL. majorplus CpG ODN with or without ALM developed few or no dermal lesions and showed an early containment of parasite growth, while mice infected withL. majorwith or without ALM developed sizable dermal lesions that required up to 10 weeks to heal. The CpG ODNs provoked a transient inflammation that included an early recruitment and accumulation of gamma interferon-producing CD4+lymphocytes in the site. Attenuation of the live vaccine did not compromise its ability to confer long-term immunity, as mice receivingL. majorand CpG ODN plus ALM were totally protected against reinfection withL. majorfor up to 6 months. By comparison, the immunity elicited by two efficient nonlive vaccines began to wane by 6 months. Our results suggest that immune modulation using CpG ODNs might be a practical approach to improving the safety of a highly effective live vaccine that has already been widely applied.
Early Induction of Humoral and Cellular Immune Responses during ExperimentalMycobacterium aviumsubsp.paratuberculosisInfection of Calves
Authors: Waters W. R. , Miller J. M. , Palmer M. V. , Stabel J. R. , Jones D. E. , Koistinen K. A. , Steadham E. M. , Hamilton M. J. , Davis W. C. , Bannantine J. P. 
Published: August 2003

ABSTRACTJohne's disease (paratuberculosis) of cattle is widespread and causes significant economic losses for producers due to decreased production and poor health of affected animals. The chronic nature of the disease and the lack of a reproducible model of infection hinder research efforts. In the present study, instillation ofMycobacterium aviumsubsp.paratuberculosisinto the tonsillar crypts of neonatal calves resulted in peripheral colonization as detected by antemortem culture of feces and postmortem (320 days postchallenge) culture of intestinal tissues. Antigen-specific blastogenic, gamma interferon (IFN-γ), and nitric oxide responses by blood mononuclear cells from infected calves exceeded prechallenge responses beginning 194 days postchallenge. Upon in vitro stimulation with paratuberculosis antigens, CD4+cells from infected calves proliferated, produced IFN-γ, and increased expression of CD26 and CD45RO (indicative of an activated memory phenotype). Utilizing a lipoarabinomannan-based enzyme-linked immunosorbent assay, specific serum immunoglobulin was detected as early as 134 days postchallenge and generally increased after this time point. Two antigens of ∼50 and ∼60 kDa were particularly immunodominant early in infection, as shown by immunoblot with serum collected within 2 weeks postchallenge. Findings indicate that the intratonsillar inoculation route will prove useful as an experimental model for paratuberculosis infection. Additionally, this study confirms that mycobacteria-specific antibody is detectable early in the course of experimental Johne's disease, even preceding the development of specific cell-mediated responses.
Lactoferrin Impairs Type III Secretory System Function in EnteropathogenicEscherichia coli
Authors: Ochoa Theresa J. , Noguera-Obenza Marita , Ebel Frank , Guzman Carlos A. , Gomez Henry F. , Cleary Thomas G. 
Published: August 2003

ABSTRACTEnteropathogenicEscherichia coli(EPEC) is an important cause of infant diarrhea in developing countries. EPEC uses a type III secretory system to deliver effector proteins into the host cell. These proteins cause the characteristic attaching and effacing lesion on enterocytes. Lactoferrin, a glycoprotein present in human milk, inhibits EPEC adherence to mammalian cells. To determine the effect of lactoferrin on the initial host cell attachment step that is mediated by the type III secretory system, we focused on EPEC-induced actin polymerization in HEp2 cells, on the hemolytic activity, and on measurement ofE. colisecreted proteins A, B, and D (EspABD). Lactoferrin blocked EPEC-mediated actin polymerization in HEp2 cells and blocked EPEC-induced hemolysis. The mechanism of this inhibition was lactoferrin-mediated degradation of secreted proteins necessary for bacterial contact and pore formation, particularly EspB. The proteolytic effect of lactoferrin was prevented by serine protease inhibitors. This disruption of the type III secretory system implies that lactoferrin could provide broad cross protection against the enteropathogens that share this mechanism.
Porphyromonas gingivalisInfection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice
Authors: Lin Dongming , Smith Mary Alice , Champagne Catherine , Elter John , Beck James , Offenbacher Steven 
Published: August 2003

ABSTRACTEpidemiological studies have shown a potential association between maternal periodontitis and pregnancy complications. We used a pregnant murine model to study the effect of infection with the periodontal pathogenPorphyromonas gingivalison pregnancy outcomes. Female BALB/c mice were inoculated with heat-killedP. gingivalis(109CFU) in a subcutaneous chamber and mated 2 weeks later. At gestation day (GD) 7.5, mice were challenged with liveP. gingivalis(107CFU) (n= 20) or broth (control;n= 8) and sacrificed at GD 16.5. Fetal growth restriction (FGR, <0.46 g) was defined as fetuses with weights 2 standard deviations (SD) smaller than controls (0.56 ± 0.05 g [mean ± SD]). Among the 20 challenged mice, 8 had both normal-weight (0.51 ± 0.11 g) and FGR (0.34 ± 0.1 g) fetuses within the same litter. All other challenged dams had normal-weight fetuses (0.57 ± 0.04 g). Maternal liver, uterus, and spleen samples were examined forP. gingivalisDNA using a PCR technique. Of the eight challenged mice with FGR fetuses, three had PCR signals forP. gingivalisin liver and uterus, but not in the spleen. Liver, uterus, and spleen were negative forP. gingivalisDNA among all other challenged and control mice. In serum of dams with FGR fetuses, tumor necrosis factor alpha levels were elevated significantly, while interluekin-10 levels were significantly reduced compared to levels in dams with normal fetuses.P. gingivalis-specific serum immunoglobulin G levels were significantly elevated in dams with FGR fetuses compared to dams without any FGR fetuses. These data demonstrate thatP. gingivalis-induced murine FGR is associated with systemic dissemination of the organism and activated maternal immune and inflammatory responses.
Insertional Inactivation ofpacandrmlBGenes Reduces the Release of Tumor Necrosis Factor Alpha, Interleukin-6, and Interleukin-8 Induced byStreptococcus mutansin Monocytic, Dental Pulp, and Periodontal Ligament Cells
Authors: Engels-Deutsch Marc , Pini Annelise , Yamashita Yoshihisa , Shibata Yukie , Haikel Youssef , Schöller-Guinard Marie , Klein Jean-Paul 
Published: August 2003

ABSTRACTStreptococcus mutanspossesses different cell wall molecules, such as protein of the I/II family, the serotype f polysaccharide rhamnose glucose polymer (RGP), and lipoteichoic acid (LTA), which act as adhesins and modulins, allowingS. mutansto colonize teeth and cause dental caries and pulpitis. We tested several isogenic mutants ofS. mutansdefective in protein I/II and/or RGP, as well as purified modulins such as protein I/II, RGP, and LTA, for their binding and activation abilities on monocytic, dental pulp (DP), and periodontal ligament (PDL) cells. Our results demonstrate that both protein I/II and RGP play important roles in streptococcal adherence to human monocytic and fibroblastic cells, whereas LTA is only a minor adhesin. In the activation process, the cytokine response elicited is polarized toward a Th1 response which seems principally due to protein I/II and RGP. Even if protein I/II seems to be more efficient in its purified form in triggering cells to release interleukin-8 (IL-8), RGP is the most efficient cytokine-stimulating component in intact bacteria, while LTA plays only a minor role. In cell activation, we showed, by using either cytochalasin D or coated ligands, that internalization of eitherS. mutans,S. mutansisogenic mutants, or purified ligands is not necessary to trigger cells to release IL-8. We also showed that, besides the implication of monocytes in pulpal inflammation, fibroblast-like cells such as DP and PDL cells are also actively implicated in local inflammation and in the generation of a Th1 response after stimulation withS. mutanscells or antigens.
Binding of Shiga Toxin 2e to Porcine Erythrocytes In Vivo and In Vitro
Authors: Matise Ilze , Cornick Nancy A. , Samuel James E. , Moon Harley W. 
Published: August 2003

ABSTRACT

Shiga toxin 2e (Stx2e), produced by host-adapted Shiga toxin-producing
Escherichia coli
(STEC) strains, causes edema disease in weaned pigs. Edema disease is manifested as vascular necrosis, edema, neurologic signs, and death. In this study we sought to determine the correlation between the presence of Stx2e in the blood of STEC-inoculated pigs and the disease outcome. Eleven of 15 (73%) pigs with clinical and 5 of 35 (14%) pigs with subclinical edema disease had detectable levels of Stx2e in the red-blood-cell (RBC) fraction of their blood but not in serum or plasma. The presence of Stx2e in the RBC fraction was strongly associated with the development of clinical disease (relative risk, 5.8;
P
< 0.0001). Subclinical pigs with Stx2e in their blood developed more-extensive vascular lesions than pigs without detectable Stx2e in their blood (average proportions of necrotic arterioles, 63 and 27.5%, respectively;
P
= 0.001). Variations in RBC-bound Stx2e levels could in part reflect variations in the binding capacity of RBCs. As an initial step toward addressing this possibility, assays were conducted to determine if pigs vary in the Stx2e binding capacity of their RBCs. An in vitro study of noninoculated pigs demonstrated two phenotypes based on the capacity of the RBCs to bind Stx2e. While RBCs from most of the pigs consistently bound high levels of Stx2e (high-binding phenotype), consistently low Stx2e binding was detected in RBCs from a few pigs (low-binding phenotype). The low- and high-binding phenotypes of individual pigs remained consistent throughout repeated samplings over 2 months.
Liposomal Meningococcal B Vaccination: Role of Dendritic Cell Targeting in the Development of a Protective Immune Response
Authors: Arigita Carmen , Bevaart Lisette , Everse Linda A. , Koning Gerben A. , Hennink Wim E. , Crommelin Daan J. A. , van de Winkel Jan G. J. , van Vugt Martine J. , Kersten Gideon F. A. , Jiskoot Wim 
Published: August 2003

ABSTRACTThe effect of targeting strategies for improving the interaction of liposomal PorA with dendritic cells (DC) on the immunogenicity of PorA was investigated. PorA, a major antigen ofNeisseria meningitidis, was purified and reconstituted in different types of (targeted) liposomes, i.e., by using mannose or phosphatidylserine as targeting moieties, or with positively charged liposomes. We studied the efficiency of liposome uptake and its effect on the maturation of and interleukin 12 (IL-12) production by murine DC. Moreover, mice were immunized subcutaneously to study the localization and immunogenicity of PorA liposomes. Uptake of liposomes by DC was significantly increased for targeted liposomes and resulted in the maturation of DC, but to various degrees. Maturation markers (i.e., CD80, CD86, major histocompatibility complex class II, and CD40) showed enhanced expression on DC incubated with targeted PorA liposomes relative to those incubated with nontargeted PorA liposomes. Moreover, only the uptake of targeted PorA liposomes induced production of IL-12 by DC, with levels similar to those produced by lipopolysaccharide (LPS)-pulsed DC. Mannose-targeted PorA liposomes administered subcutaneously had an increased localization in draining lymph nodes compared to nontargeted PorA liposomes. Liposomes in draining lymph nodes interacted preferentially with antigen-presenting cells, an effect that was enhanced with targeted PorA liposomes. Immunization studies showed an improvement of the bactericidal antibody response (i.e., increased number of responders) generated by targeted PorA liposomes compared to that generated by nontargeted ones or LPS-containing outer membrane vesicles. In conclusion, the use of targeted PorA liposomes results in an improved uptake by and activation of DC and an increased localization in draining lymph nodes. These effects correlate with an enhanced immune response toward the vaccine.
Unusual Interaction of a Lipopolysaccharide Isolated fromBurkholderia cepaciawith Polymyxin B
Authors: Shimomura Hirofumi , Matsuura Motohiro , Saito Shinji , Hirai Yoshikazu , Isshiki Yasunori , Kawahara Kazuyoshi 
Published: August 2003

ABSTRACTWe have demonstrated that lipopolysaccharide (LPS) obtained fromBurkholderia cepacia, an important opportunistic pathogen, has unique characteristics in both structure and activity. One of the structural characteristics is that theB. cepaciaLPS has 4-amino-4-deoxy-l-arabinose (Ara4N) in its inner core region. Polymyxin B (PmxB) is known to act as an LPS antagonist, but LPS with Ara4N is suggested to be PmxB resistant by decreasing the binding capability of PmxB. Interaction ofB. cepaciaLPS with PmxB was investigated and compared with that of a reference LPS ofSalmonella entericaserovar Abortusequi, referred to hereafter as the reference LPS.B. cepaciaLPS suffered no suppressive effect of PmxB in its activity to stimulate murine peritoneal macrophages for induction of tumor necrosis factor alpha (TNF-α) and IL-6 even when the activity of the reference LPS was completely suppressed. A characteristic ofB. cepaciaLPS is that it has selectively weak interleukin-1β (IL-1β)-inducing activity while activity to induce TNF-α and IL-6 has been shown to be as strong as that of the reference LPS. Remarkably, PmxB augmented the IL-1β-inducing activity ofB. cepaciaLPS to the level of that of the reference LPS and, in contrast, completely suppressed the strong activity of the reference LPS. Using PmxB-immobilized beads, the adsorbances of these LPSs to the beads were compared, and it was found thatB. cepaciaLPS bound to PmxB with a high affinity similar to that of the reference LPS. These results indicate an unusual interaction ofB. cepaciaLPS with PmxB wherebyB. cepaciaLPS not only allows the binding of PmxB with high affinity, even though it contains Ara4N, but also suffers no suppressive effect of PmxB on its activity. Moreover, a remarkable increase in its IL-1β-inducing activity was also observed.
Influence of Maternal Filariasis on Childhood Infection and Immunity toWuchereria bancroftiin Kenya
Authors: Malhotra Indu , Ouma John H. , Wamachi Alex , Kioko John , Mungai Peter , Njzovu Malik , Kazura James W. , King Christopher L. 
Published: August 2003

ABSTRACTTo determine whether maternal filariasis influences the risk of infection by and immunity toWuchereria bancroftiin children, we performed a cross-sectional study in an area of Kenya where filariasis is endemic. Residents of 211 households were enrolled; 376 parents and 938 of their offspring between the ages of 2 and 17 years were examined for filarial infection status as determined by blood-borne microfilariae and filarial antigenemia. Children of infected mothers had a three- to fourfold increased risk of filarial infection, as ascertained by circulating filarial antigen, relative to children of uninfected mothers (P< 0.001). Paternal infection did not correlate with childhood infection status, indicating a specific maternal effect. Peripheral blood mononuclear cells from children of filaria-infected mothers (n= 33) had higher levels of constitutive interleukin-5 (IL-5) and IL-10, increased microfilarial antigen-specific IL-5 production, and diminished microfilarial antigen-driven lymphocyte proliferation than cells from children of uninfected mothers (n= 46;P< 0.05). In contrast, there were no differences between the two groups in adult worm antigen-driven gamma interferon, IL-2, IL-4, IL-5, and IL-10 production and lymphocyte proliferation. These data indicate that maternal filarial infection increases childhood susceptibility toW. bancroftiand skews filaria-specific immunity toward a Th2-type cytokine response. The results support the notion that in utero exposure to filarial antigens affects the natural history of filariasis during childhood.