bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased In Situ Expression of Interleukin-10 Receptor Is Correlated with the Exacerbated Inflammatory and Cytotoxic Responses Observed in Mucosal Leishmaniasis
Authors: Faria Daniela R. , Gollob Kenneth J. , Barbosa José , Schriefer Albert , Machado Paulo R. L. , Lessa Hélio , Carvalho Lucas P. , Romano-Silva Marco Aurélio , de Jesus Amélia R. , Carvalho Edgar M. , Dutra Walderez O. 
Published: November 2005

ABSTRACTHuman infection withLeishmania braziliensiscan lead to cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML). We hypothesize that the intense tissue destruction observed in ML is a consequence of an uncontrolled exacerbated inflammatory immune response, with cytotoxic activity. For the first time, this work identifies the cellular sources of inflammatory and antiinflammatory cytokines, the expression of effector molecules, and the expression of interleukin-10 (IL-10) receptor in ML and CL lesions by using confocal microscopy. ML lesions displayed a higher number of gamma interferon (IFN-γ)-producing cells than did CL lesions. In both ML and CL, CD4+cells represented the majority of IFN-γ-producing cells, followed by CD8+cells and CD4−CD8−cells. The numbers of tumor necrosis factor alpha-positive cells, as well as those of IL-10-producing cells, were similar in ML and CL lesions. The effector molecule granzyme A showed greater expression in ML than in CL lesions, while inducible nitric oxide synthase did not. Finally, the expression of IL-10 receptor was lower in ML than in CL lesions. Thus, our data identified distinct cytokine and cell population profiles for CL versus ML patients and provide a possible mechanism for the development of ML disease through the demonstration that low expression of IL-10 receptor is present in conjunction with a cytotoxic and inflammatory profile in ML.
Active and Passive Intranasal Immunizations with Streptococcal Surface Protein C5a Peptidase Prevent Infection of Murine Nasal Mucosa-Associated Lymphoid Tissue, a Functional Homologue of Human Tonsils
Authors: Park Hae-Sun , Cleary P. Patrick 
Published: November 2005

ABSTRACT
C5a peptidase, also called SCPA (surface-bound C5a peptidase), is a surface-bound protein on group A streptococci (GAS), etiologic agents for a variety of human diseases including pharyngitis, impetigo, toxic shock, and necrotizing fasciitis, as well as the postinfection sequelae rheumatic fever and rheumatic heart disease. This protein is highly conserved among different serotypes and is also expressed in human isolates of group B, C, and G streptococci. Human tonsils are the primary reservoirs for GAS, maintaining endemic disease across the globe. We recently reported that GAS preferentially target nasal mucosa-associated lymphoid tissue (NALT) in mice, a tissue functionally analogous to human tonsils. Experiments using a C5a peptidase loss-of-function mutant and an intranasal infection model showed that this protease is required for efficient colonization of NALT. An effective vaccine should prevent infection of this secondary lymphoid tissue; therefore, the potential of anti-SCPA antibodies to protect against streptococcal infection of NALT was investigated. Experiments showed that GAS colonization of NALT was significantly reduced following intranasal immunization of mice with recombinant SCPA protein administered alone or with cholera toxin, whereas a high degree of GAS colonization of NALT was observed in control mice immunized with phosphate-buffered saline only. Moreover, administration of anti-SCPA serum by the intranasal route protected mice against streptococcal infection. These results suggest that intranasal immunization with SCPA would prevent colonization and infection of human tonsils, thereby eliminating potential reservoirs that maintain endemic disease.
Conjugates of Group A and W135 Capsular Polysaccharides ofNeisseria meningitidisBound to RecombinantStaphylococcus aureusEnterotoxin C1: Preparation, Physicochemical Characterization, and Immunological Properties in Mice
Authors: Jin Zhigang , Bohach Gregory A. , Shiloach Joseph , Norris Scott E. , Freedberg Darón I. , Deobald Claudia , Coxon Bruce , Robbins John B. , Schneerson Rachel 
Published: November 2005

ABSTRACTNeisseria meningitidisgroups A (GAM) and W135 capsular polysaccharides (CPs) were bound to recombinantStaphylococcus aureusenterotoxin C1 (rSEC). The CPs were activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate and then bound to adipic acid dihydrazide derivatives ofrSEC. Syntheses were conducted with native GAM CP (GAMP), W135 CP (W135P), and ultrasonicated or hydrazine-treated W135P at various concentrations of reactants, pHs, and ionic strengths. The conjugates were characterized by compositional and serologic analyses, high-performance size-exclusion chromatography with multi-angle laser light scattering detection, and immunogenicity in 5- to 6-week-old mice. Conjugates injected subcutaneously in phosphate-buffered saline elicited immunoglobulin G (IgG) responses against their respective CPs andrSEC, whereas GAMP and W135P alone did not induce detectable CP antibodies. The O-acetyl content of W135P was low, and its removal had no adverse effect upon the conjugate's immunogenicity. Reduction of the molecular size of W135P by treatment with hydrazine improved the immunogenicity of W135P-rSEC. IgG anti-CP elicited by the conjugates showed complement-dependent bactericidal activity against their respective organisms, and IgG anti-rSEC neutralized the T-cell proliferative activity of native SEC. A bivalent formulation of GAMP-rSEC and W135P-rSEC elicited IgG anti-CP at comparable levels to those induced by the conjugates administered separately.
Identification of Core and Variable Components of the
Salmonella enterica
Subspecies I Genome by Microarray
Authors: Anjum Muna F. , Marooney Chris , Fookes Maria , Baker Stephen , Dougan Gordon , Ivens Al , Woodward Martin J. 
Published: November 2005

ABSTRACT

We have performed microarray hybridization studies on 40 clinical isolates from 12 common serovars within
Salmonella enterica
subspecies I to identify the conserved chromosomal gene pool. We were able to separate the core invariant portion of the genome by a novel mathematical approach using a decision tree based on genes ranked by increasing variance. All genes within the core component were confirmed using available sequence and microarray information for
S. enterica
subspecies I strains. The majority of genes within the core component had conserved homologues in
Escherichia coli
K-12 strain MG1655. However, many genes present in the conserved set which were absent or highly divergent in K-12 had close homologues in pathogenic bacteria such as
Shigella flexneri
and
Pseudomonas aeruginosa
. Genes within previously established virulence determinants such as SPI1 to SPI5 were conserved. In addition several genes within SPI6, all of SPI9, and three fimbrial operons (
fim
,
bcf
, and
stb
) were conserved within all
S. enterica
strains included in this study. Although many phage and insertion sequence elements were missing from the core component, approximately half the pseudogenes present in
S. enterica
serovar Typhi were conserved. Furthermore, approximately half the genes conserved in the core set encoded hypothetical proteins. Separation of the core and variant gene sets within
S.enterica
subspecies I has offered fundamental biological insight into the genetic basis of phenotypic similarity and diversity across
S. enterica
subspecies I and shown how the core genome of these pathogens differs from the closely related
E. coli
K-12 laboratory strain.
Syndecan 1 Shedding Contributes to
Pseudomonas aeruginosa
Sepsis
Authors: Haynes Allan , Ruda Frank , Oliver Jeffrey , Hamood Abdul N. , Griswold John A. , Park Pyong Woo , Rumbaugh Kendra P. 
Published: November 2005

ABSTRACT

The innate immune system is comprised of many components that function coordinately to prevent bacterial sepsis. However, thermal injury suppresses many of these factors, and the opportunistic pathogen
Pseudomonas aeruginosa
takes advantage of this condition, making it one of the leading causes of morbidity and mortality in the setting of thermal injury.
P. aeruginosa
is extremely efficient at colonizing burn wounds, spreading systemically, and causing sepsis, which often results in a systemic inflammatory response, multiple-organ failure, and death. The pathogenicity of
P. aeruginosa
is due to the arsenal of virulence factors produced by the pathogen and the immunocompromised state of the host. Syndecan 1 is a major heparan sulfate proteoglycan present on many host cells involved in thermal injury. Syndecan 1 anchored to the cell surface can be cleaved in a process termed ectodomain shedding. Syndecan 1 shedding results in the release of intact, soluble proteoglycan ectodomains that have diverse roles in innate immunity. Here we show for the first time that thermal injury results in shedding of syndecan 1 from host tissue. Our data show that syndecan 1 null mice are significantly less susceptible to
P. aeruginosa
infection than their wild-type counterparts, as demonstrated by (i) significantly lower mortality; (ii) absence of systemic spread of
P. aeruginosa
; and (iii) significant reductions in some proinflammatory cytokines. These results suggest that shed syndecan 1 plays an important role in the pathogenesis of
P. aeruginosa
infection of thermal injury and that syndecan 1-neutralizing agents may be effective supplements to current
P. aeruginosa
treatments.
Tissue Destruction Induced by
Porphyromonas gingivalis
Infection in a Mouse Chamber Model Is Associated with Host Tumor Necrosis Factor Generation
Authors: Lin Yuh-Yih , Huang Jan-Hung , Lai Yo-Yin , Huang Han-Ching , Hu Suh-Woan 
Published: November 2005

ABSTRACT

Intrachamber challenge with
Porphyromonas gingivalis
strain 381 in a mouse subcutaneous chamber model results in a local infection that progresses to exfoliation of the chambers within 15 days. This study was designed to elucidate the contribution of host reactions to tissue destruction manifested by chamber exfoliation in animals infected with
P. gingivalis
. Chamber fluids showed increasing levels of prostaglandin E
2
with infection, and the levels of tumor necrosis factor (TNF) in chamber fluids peaked just before chamber exfoliation. Intraperitoneal injection of a TNF inhibitor, thalidomide (TH), reduced the number of exfoliated chambers, while indomethacin had no effect. Exogenous TNF in chambers without bacterial infection did not cause chamber exfoliation but induced neutrophil infiltration. In a dual-chamber model, two chambers were implanted in the same mouse. One chamber was infected with
P. gingivalis
, and 9 days later exogenous TNF was added to the other chamber. Altogether, 66.67% of uninfected chambers were exfoliated between day 11 and day 16, although no bacteria were recovered from uninfected chambers. TH treatment alleviated both infected and uninfected chamber exfoliation. In this study, tissue destruction caused by
P. gingivalis
381 infection was due to the elevation of the TNF levels and not due to local bacterial activities. Our results further indicate that local infection by
P. gingivalis
381, a nondisseminating strain, actually has systemic effects on the host pathological outcome.
Increased Sensitivity toSalmonella entericaSerovar Typhimurium Infection in Mice Undergoing Withdrawal from Morphine Is Associated with Suppression of Interleukin-12
Authors: Feng Pu , Wilson Qiana M. , Meissler Joseph J. , Adler Martin W. , Eisenstein Toby K. 
Published: November 2005

ABSTRACTWe have shown previously that withdrawal from morphine induces immunosuppression in mice. The present study reports the effects of morphine withdrawal on infection withSalmonella entericaserovar Typhimurium. Mice were made dependent on morphine by the implantation of a slow-release morphine pellet for 96 h. Controls received a placebo pellet. Withdrawal was induced by pellet removal. Mice were inoculated intraperitoneally withSalmonella24 h postwithdrawal. Morphine withdrawal sensitized mice toSalmonellainfection, as evidenced by increased mortality, shortened mean survival time, and increased bacterial load in the blood, spleen, and liver. Examination of the levels of a panel of proinflammatory cytokines in sera of infected, morphine-withdrawn mice showed that morphine withdrawal inhibited the elevation of interleukin-12p70 (IL-12p70). The production of IL-12p40 in morphine withdrawal mice was also suppressed. The administration of exogenous IL-12 significantly decreased the bacterial burden in morphine-withdrawn mice. These studies show a correlation between the suppression of IL-12 production and a heightened susceptibility toSalmonellainfection in mice undergoing withdrawal from morphine.
Type 1 Chemokine Receptor Expression in Chagas' Disease Correlates with Morbidity in Cardiac Patients
Authors: Gomes Juliana A. S. , Bahia-Oliveira Lilian M. G. , Rocha Manoel Otávio C. , Busek Solange C. U. , Teixeira Mauro M. , Silva João Santana , Correa-Oliveira Rodrigo 
Published: November 2005

ABSTRACTChemokines and chemokine receptors (CKRs) control the migration of leukocytes during the inflammatory process and are important immunological markers of type 1 (CCR5 and CXCR3) and type 2 (CCR3 and CCR4) responses. The coexpression of CKRs (CCR2, CCR3, CCR5, CXCR3, and CXCR4) and intracellular cytokines (interleukin-10 [IL-10], IL-4, tumor necrosis factor alpha [TNF-α], and gamma interferon [IFN-γ]) on T CD4+and CD8+peripheral cells from individuals with indeterminate (IND) or cardiac (CARD) clinical forms of Chagas' disease after in vitro stimulation withTrypanosoma cruziantigens, were evaluated in this study. The percentage of T CD4+and CD8+cells coexpressing CCR5 and IFN-γ, CXCR3 and IFN-γ, and CXCR3 and TNF-α were higher in CARD than in IND individuals; on the other hand, the percentage of T CD4+or CD8+cells coexpressing CCR3 and IL-10 or coexpressing CCR3 and IL-4 were lower in CARD individuals than in IND individuals. In addition, a significant positive correlation between the expression of CCR5 or CXCR3 and IFN-γ was observed in CARD individuals contrasting with a significant positive correlation between the expression of CCR3 and IL-4 and of CCR3 and IL-10 in IND patients. These results reinforce the hypothesis that aT. cruzi-exacerbated specific type 1 immune response developed by CARD chagasic patients is associated with the development of heart pathology.
Synergistic Effect of Nod1 and Nod2 Agonists with Toll-Like Receptor Agonists on Human Dendritic Cells To Generate Interleukin-12 and T Helper Type 1 Cells
Authors: Tada Hiroyuki , Aiba Setsuya , Shibata Ken-Ichiro , Ohteki Toshiaki , Takada Haruhiko 
Published: November 2005

ABSTRACTA synthetic Nod2 agonist, muramyldipeptide (MDP), and two Nod1 agonists, FK565 and FK156, mimic the bacterial peptidoglycan moiety and are powerful adjuvants that induce cell-mediated immunity, especially delayed-type hypersensitivity. In this study, we used human dendritic cell (DC) cultures to examine possible T helper type 1 (Th1) responses induced by MDP and FK565/156 in combination with various synthetic Toll-like receptor (TLR) agonists, including synthetic lipid A (TLR4 agonist), the synthetic triacyl lipopeptide Pam3CSSNA (TLR2 agonist), poly(I:C) (TLR3 agonist), and CpG DNA (TLR9 agonist). Immature DCs derived from human monocytes expressed mRNAs for Nod1, Nod2, TLR2, TLR3, TLR4, and TLR9. The stimulation of DCs with MDP and FK565 in combination with lipid A, poly(I:C), and CpG DNA, but not with Pam3CSSNA, synergistically induced interleukin-12 (IL-12) p70 and gamma interferon (IFN-γ), but not IL-18, in culture supernatants and induced IL-15 on the cell surface. In correlation with the cytokine induction, an upregulation of the mRNA expression of these cytokine genes was observed. Notably, IL-12 p35 mRNA expression increased >1,000-fold upon stimulation with lipid A plus either MDP or FK565 compared with stimulation with each stimulant alone. In contrast, for the expression of CD83 and costimulatory molecules such as CD40, CD80, and CD86, no synergistic effects were observed upon stimulation with Nod plus TLR agonists. The culture supernatants of DCs stimulated with lipid A plus either MDP or FK565 activated human T cells to produce high levels of IFN-γ, and the activity was attributable to DC-derived IL-12. These findings suggest that Nod1 and Nod2 agonists in combination with TLR3, TLR4, and TLR9 agonists synergistically induce IL-12 and IFN-γ production in DCs to induce Th1-lineage immune responses.
Deletions of Endocytic Components
VPS28
and
VPS32
Affect Growth at Alkaline pH and Virulence through both
RIM101
-Dependent and
RIM101
-Independent Pathways in
Candida albicans
Authors: Cornet Muriel , Bidard Frédérique , Schwarz Patrick , Da Costa Grégory , Blanchin-Roland Sylvie , Dromer Françoise , Gaillardin Claude 
Published: November 2005

ABSTRACT

Ambient pH signaling involves a cascade of conserved Rim or Pal products in ascomycetous yeasts or filamentous fungi, respectively. Recent evidences in the fungi
Aspergillus nidulans
,
Saccharomyces cerevisiae
,
Yarrowia lipolytica
, and
Candida albicans
suggested that components of endosomal sorting complexes required for transport (ESCRT) involved in endocytic trafficking were needed for signal transduction along the Rim pathway. In this study, we confirm these findings with
C. albicans
and show that Vps28p (ESCRT-I) and Vps32p/Snf7p (ESCRT-III) are required for the transcriptional regulation of known targets of the Rim pathway, such as the
PHR1
and
PHR2
genes encoding cell surface proteins, which are expressed at alkaline and acidic pH, respectively. We additionally show that deletion of these two
VPS
genes, particularly
VPS32
, has a more drastic effect than a
RIM101
deletion on growth at alkaline pH and that this effect is only partially suppressed by expression of a constitutively active form of Rim101p. Finally, in an in vivo mouse model, both
vps
null mutants were significantly less virulent than a
rim101
mutant, suggesting that
VPS28
and
VPS32
gene products affect virulence both through Rim-dependent and Rim-independent pathways.
Chronic
Leishmania donovani
Infection Promotes Bystander CD8
+
-T-Cell Expansion and Heterologous Immunity
Authors: Polley Rosalind , Sanos Stephanie L. , Prickett Sara , Haque Ashraful , Kaye Paul M. 
Published: November 2005

ABSTRACT

It has been proposed that long-lived memory T cells generated by vaccination or infection reside within a memory compartment that has a finite size. Consequently, in a variety of acute infection models interclonal competition has been shown to lead to attrition of preexisting memory CD8
+
T cells. Contrary to expectations, therefore, we found that chronic
Leishmania donovani
infection of
Listeria
-immune mice results in heightened protection against subsequent
Listeria
challenge. This protection was associated with bystander expansion of
Listeria
-specific CD8
+
T cells and a bias in these cells toward a central memory T-cell phenotype with an enhanced capacity for gamma interferon production. We propose that splenomegaly, which is characteristic of visceral leishmaniasis and other tropical infections, may help promote heterologous immunity by resetting the size of the memory compartment during chronic infection.
H2-M3 Major Histocompatibility Complex Class Ib-Restricted CD8 T Cells Induced bySalmonella entericaSerovar Typhimurium Infection Recognize Proteins Released bySalmonellaSerovar Typhimurium
Authors: Ugrinovic S. , Brooks C. G. , Robson J. , Blacklaws B. A. , Hormaeche C. E. , Robinson J. H. 
Published: November 2005

ABSTRACTSalmonella entericaserovar Typhimurium causes a typhoid-like disease in mice which has been studied extensively as a model for typhoid fever in humans. CD8 T cells contribute to protection againstS. entericaserovar Typhimurium in mice, but little is known about the specificity and major histocompatibility complex (MHC) restriction of the response. We report here that CD8 T-cell lines derived fromS. entericaserovar Typhimurium-infected BALB/c mice lysed bone marrow macrophages infected withS. entericaserovar Typhimurium or pulsed with proteins fromS. entericaserovar Typhimurium culture supernatants. Cytoxicity was beta-2-microglobulin dependent and largely TAP dependent, although not MHC class Ia restricted, as target cells of several different MHC haplotypes were lysed. The data suggested the participation of class Ib MHC molecules although no evidence for the presence of Qa1-restricted T cells could be found, unlike in previous reports. Instead, the T-cell lines lysed H2-M3-transfected fibroblasts infected withS. entericaserovar Typhimurium SL3261 or treated withSalmonellaculture supernatants. Thus, this report increases the number of MHC class Ib antigen-presenting molecules known forSalmonellaantigens to three: Qa-1, HLA-E, and now H2-M3. It also expands the range of pathogens that induce H2-M3-restricted CD8 T cells to include an example of gram-negative bacteria.
Essential Role for Humoral Immunity duringEhrlichiaInfection in Immunocompetent Mice
Authors: Yager Eric , Bitsaktsis Constantine , Nandi Bisweswar , McBride Jere W. , Winslow Gary 
Published: November 2005

ABSTRACTAlthough cellular immunity is essential for host defense during intracellular bacterial infections, humoral immunity can also play a significant role in host defense during infection by some intracellular bacteria, including the ehrlichiae. Antibodies can protect susceptible SCID mice from fatalEhrlichia chaffeensisinfection, an observation that has been hypothesized to involve the opsonization of bacteria released from host cells. To determine whether humoral immunity plays an essential role during ehrlichia infection in immunocompetent mice, we utilized a murine model of fatal monocytotropic ehrlichiosis caused byIxodes ovatusehrlichia. Mice lacking either B cells or FcγRI were unable to resolve a low-dose (sublethal)I. ovatusehrlichia infection, which suggested that humoral immunity is essential for resistance. Polyclonal sera generated inI. ovatusehrlichia-infected mice recognized a conserved ehrlichia outer membrane protein and, when administered to infected mice, caused a significant decrease in bacterial infection. Mice experimentally depleted of complement, or deficient for complement receptors 1 and 2, were also susceptible to sublethalI. ovatusehrlichia infection, as were mice that lacked the phox91 subunit of NADPH oxidase. The data are consistent with a mechanism whereby bacteria released from infected cells are lysed directly by complement or undergo antibody-mediated FcγR-dependent phagocytosis and subsequent exposure to reactive oxygen intermediates. The findings suggest mechanisms whereby antibodies contribute to immunity against intracellular bacteria in immunocompetent mice.