bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Serum Cytokines in Patients with Severe Acute Respiratory Syndrome
Authors: Zhang Yuanchun , Li Jing , Zhan Yuliang , Wu Lianqiu , Yu Xueying , Zhang Wenjian , Ye Liya , Xu Shiqing , Sun Ruihua , Wang Yunting , Lou Jinning 
Published: July 2004

ABSTRACT
Severe acute respiratory syndrome (SARS) is an acute infectious disease of the respiratory system. Although a novel coronavirus has been identified as the causative agent of SARS, the pathogenic mechanisms of SARS are not understood. In this study, sera were collected from healthy donors, patients with SARS, patients with severe SARS, and patients with SARS in convalescence. The serum concentrations of interleukin-1 (IL-1), IL-4, IL-6, IL-8, IL-10, tumor growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) were measured by enzyme-linked immunosorbent assays (ELISA). The concentrations of IL-1 and TNF-α were not significantly different in different groups. The IL-6 concentration was increased in SARS patients and was significantly elevated in severe SARS patients, but the IL-6 concentrations were similar in convalescent patients and control subjects, suggesting that there was a positive relationship between the serum IL-6 concentration and SARS severity. The concentrations of IL-8 and TGF-β were decreased in SARS patients and significantly reduced in severe SARS patients, but they were comparable in convalescent SARS patients and control subjects, suggesting that there was a negative relationship between the IL-8 and TGF-β concentrations and SARS severity. The concentrations of IFN-γ, IL-4, and IL-10 showed significant changes only in convalescent SARS patients. The IFN-γ and IL-4 levels were decreased, while the levels of IL-10 were increased, and the differences between convalescent SARS patients and other patient groups were statistically significant. These results suggest that there are different immunoregulatory events during and after SARS and may contribute to our understanding of the pathogenesis of this syndrome.
Effects of the
Enterococcus faecalis hypR
Gene Encoding a New Transcriptional Regulator on Oxidative Stress Response and Intracellular Survival within Macrophages
Authors: Verneuil Nicolas , Sanguinetti Maurizio , Le Breton Yoann , Posteraro Brunella , Fadda Giovanni , Auffray Yanick , Hartke Axel , Giard Jean-Christophe 
Published: July 2004

ABSTRACT

In order to identify regulators of the oxidative stress response in
Enterococcus faecalis
, an important human pathogen, several genes annotated as coding for transcriptional regulators were inactivated by insertional mutagenesis. One mutant, affected in the
ef2958
locus (designated
hypR
[hydrogen peroxide regulator]), appeared to be highly sensitive to oxidative challenge caused by hydrogen peroxide. Moreover, testing of the
hypR
mutant by using an in vivo-in vitro macrophage infection model resulted in a highly significant reduction in survival compared to the survival of parent strain JH2-2. Northern blot analyses were carried out with probes specific for genes encoding known antioxidant enzymes, and they showed that the
ahpCF
(alkyl hydro

p

eroxide reductase) transcript was expressed less in mutant cells. Mobility shift protein-DNA binding assays revealed that HypR regulated directly the expression of
hypR
itself and the
ahpCF
operon. Our combined results showed that HypR appeared to be directly involved in the expression of
ahpCF
genes under oxidative stress conditions and suggested that this regulator could contribute to the virulence of
E. faecalis
.
Gamma Interferon Production, but Not Perforin-Mediated Cytolytic Activity, of T Cells Is Required for Prevention of Toxoplasmic Encephalitis in BALB/c Mice Genetically Resistant to the Disease
Authors: Wang Xisheng , Kang Hoil , Kikuchi Takane , Suzuki Yasuhiro 
Published: July 2004

ABSTRACTWe previously showed the requirement of both T cells and gamma interferon (IFN-γ)-producing non-T cells for the genetic resistance of BALB/c mice to the development of toxoplasmic encephalitis (TE). In order to define the role of IFN-γ production and the perforin-mediated cytotoxicity of T cells in this resistance, we obtained immune T cells from spleens of infected IFN-γ knockout (IFN-γ−/−), perforin knockout (PO), and wild-type BALB/c mice and transferred them into infected and sulfadiazine-treated athymic nude mice, which lack T cells but have IFN-γ-producing non-T cells. Control nude mice that had not received any T cells developed severe TE and died after discontinuation of sulfadiazine treatment due to the reactivation of infection. Animals that had received immune T cells from either wild-type or PO mice did not develop TE and survived. In contrast, nude mice that had received immune T cells from IFN-γ−/−mice developed severe TE and died as early as control nude mice. T cells obtained from the spleens of animals that had received either PO or wild-type T cells produced large amounts of IFN-γ after stimulation withToxoplasma gondiiantigens in vitro. In addition, the amounts of IFN-γ mRNA expressed in the brains of PO T-cell recipients did not differ from those in wild-type T-cell recipients. Furthermore, PO mice did not develop TE after infection, and their IFN-γ production was equivalent to or higher than that of wild-type animals. These results indicate that IFN-γ production, but not perforin-mediated cytotoxic activity, by T cells is required for the prevention of TE in genetically resistant BALB/c mice.
The Major Subunit of the Toxin-Coregulated Pilus TcpA Induces Mucosal and Systemic Immunoglobulin A Immune Responses in Patients with Cholera Caused by
Vibrio cholerae
O1 and O139
Authors: Asaduzzaman Muhammad , Ryan Edward T. , John Manohar , Hang Long , Khan Ashraful I. , Faruque A. S. G. , Taylor Ronald K. , Calderwood Stephen B. , Qadri Firdausi 
Published: July 2004

ABSTRACT

Diarrhea caused by
Vibrio cholerae
is known to give long-lasting protection against subsequent life-threatening illness. The serum vibriocidal antibody response has been well studied and has been shown to correlate with protection. However, this systemic antibody response may be a surrogate marker for mucosal immune responses to key colonization factors of this organism, such as the toxin-coregulated pilus (TCP) and other factors. Information regarding immune responses to TCP, particularly mucosal immune responses, is lacking, particularly for patients infected with the El Tor biotype of
V. cholerae
O1 or
V. cholerae
O139 since highly purified TcpA from these strains has not been available previously for use in immune assays. We studied the immune responses to El Tor TcpA in cholera patients in Bangladesh. Patients had substantial and significant increases in TcpA-specific antibody-secreting cells in the circulation on day 7 after the onset of illness, as well as similar mucosal responses as determined by an alternate technique, the assay for antibody in lymphocyte supernatant. Significant increases in antibodies to TcpA were also seen in sera and feces of patients on days 7 and 21 after the onset of infection. Overall, 93% of the patients showed a TcpA-specific response in at least one of the specimens compared with the results obtained on day 2 and with healthy controls. These results demonstrate that TcpA is immunogenic following natural
V. cholerae
infection and suggest that immune responses to this antigen should be evaluated for potential protection against subsequent life-threatening illness.
Helicobacter pylori
Induces Apoptosis of Human Monocytes but Not Monocyte-Derived Dendritic Cells: Role of the
cag
Pathogenicity Island
Authors: Galgani Mario , Busiello Immacolata , Censini Stefano , Zappacosta Serafino , Racioppi Luigi , Zarrilli Raffaele 
Published: July 2004

ABSTRACT

Monocytes are circulating precursors of the dendritic cell subset, professional antigen-presenting cells with a unique ability to initiate the innate and adaptive immune response. In this study, we have investigated the effects of wild-type
Helicobacter pylori
strains and their isogenic mutants with mutations in known bacterial virulence factors on monocytes and monocyte-derived dendritic cells. We show that
H. pylori
strains induce apoptosis of human monocytes by a mechanism that is dependent on the expression of a functional
cag
pathogenicity island. This effect requires an intact injection organelle for direct contact between monocytes and the bacteria but also requires a still-unidentified effector that is different from VacA or CagA. The exposure of in vitro-generated monocyte-derived dendritic cells to
H. pylori
stimulates the release of inflammatory cytokines by a similar mechanism. Of note is that dendritic cells are resistant to
H. pylori
-induced apoptosis. These phenomena may play a critical role in the evasion of the immune response by
H. pylori
, contributing to the persistence of the infection.
Characterization of an I-E-Restricted, gp63-Specific, CD4-T-Cell Clone fromLeishmania major-Resistant C3H Mice That Secretes Type 2 Cytokines and Exacerbates Infection withL. major
Authors: Theodos Cynthia M. , Morris Robin V. , Bishop Jeanette V. , Jones Jeremy D. , McMaster W. Robert , Titus Richard G. 
Published: July 2004

ABSTRACTA T-cell clone (designated KLmB-3) was derived from resistant C3H mice 2 weeks after infection withLeishmania major. KLmB-3 was a CD4-T-cell clone that utilized the Vβ8.1 T-cell receptor. When adoptively transferred to naive C3H mice, KLmB-3 unexpectedly exacerbated infection withL. major(it increased the cutaneous lesion size and the parasite burden within the lesion). The ability of KLmB-3 to exacerbate disease correlated with its ability to produce the type 2-associated cytokines interleukin-4 (IL-4), IL-5, IL-10, and transforming growth factor beta. Interestingly, KLmB-3 was specific for an epitope in the amino-terminal end of theL. majorsurface gp63 zinc metalloproteinase (leishmanolysin) that has been shown to be capable of inducing a protective immune response. Moreover, KLmB-3 was activated when this epitope was presented in the context of H-2 I-E rather than H-2 I-A.
Cytotoxicity of Hydrogen Peroxide Produced by
Enterococcus faecium
Authors: Moy Terence I. , Mylonakis Eleftherios , Calderwood Stephen B. , Ausubel Frederick M. 
Published: July 2004

ABSTRACT

Although the opportunistic bacterial pathogen
Enterococcus faecium
is a leading source of nosocomial infections, it appears to lack many of the overt virulence factors produced by other bacterial pathogens, and the underlying mechanism of pathogenesis is not clear. Using
E. faecium
-mediated killing of the nematode worm
Caenorhabditis elegans
as an indicator of toxicity, we determined that
E. faecium
produces hydrogen peroxide at levels that cause cellular damage. We identified
E. faecium
transposon insertion mutants with altered
C. elegans
killing activity, and these mutants were altered in hydrogen peroxide production. Mutation of an NADH oxidase-encoding gene eliminated nearly all NADH oxidase activity and reduced hydrogen peroxide production. Mutation of an NADH peroxidase-encoding gene resulted in the enhanced accumulation of hydrogen peroxide.
E. faecium
is able to produce hydrogen peroxide by using glycerol-3-phosphate oxidase, and addition of glycerol to the culture medium enhanced the killing of
C. elegans
. Conversely, addition of glucose, which leads to the down-regulation of glycerol metabolism, prevented both
C. elegans
killing and hydrogen peroxide production. Lastly, detoxification of hydrogen peroxide either by exogenously added catalase or by a
C. elegans
transgenic strain overproducing catalase prevented
E. faecium
-mediated killing. These results suggest that hydrogen peroxide produced by
E. faecium
has cytotoxic effects and highlight the utility of
C. elegans
pathogenicity models for identifying bacterial virulence factors.
The Plague Virulence Protein YopM Targets the Innate Immune Response by Causing a Global Depletion of NK Cells
Authors: Kerschen Edward J. , Cohen Donald A. , Kaplan Alan M. , Straley Susan C. 
Published: July 2004

ABSTRACTYersinia pestis, the etiologic agent of plague, delivers sixYersiniaouter proteins (Yops) into host cells upon direct bacterial contact. One of these, YopM, is necessary for virulence in a mouse model of septicemic plague, but its pathogenic function is unknown. We report here the immune processes affected by YopM during infection. To test whether the innate or adaptive immune system is targeted by YopM, C57BL/6 (B6) and B6 SCID mice were infected with either the conditionally virulentY. pestisKIM5 or ayopMdeletion mutant and evaluated for bacterial growth in spleen and liver. Both B6 and SCID mice succumbed to infection withY. pestisKIM5, whereas both mouse strains survived infection by the YopM−mutant. These data showed that YopM counteracts innate defenses present in SCID mice. The YopM−strain grew more slowly than the parentY. pestisduring the first 4 days of infection in both mouse strains, indicating an early pathogenic role for YopM. In B6 mice, populations of cells of the immune system were not differentially affected by the twoY. pestisstrains, with one major exception: the parentY. pestisKIM5 but not the YopM−mutant caused a significant global decrease in NK cell numbers (blood, spleen, and liver), beginning early in infection. NK cells and macrophages isolated early (day 2) from livers and spleens of mice infected with eitherY. pestisstrain contained comparable levels of cytokine mRNA: interleukin (IL)-1β, IL-12, IL-15, IL-18, and tumor necrosis factor alpha in macrophages and gamma interferon in NK cells. However, by day 4 postinfection, cells from mice infected with the parentY. pestisexpressed lower levels of these messages, while those from mice infected with the mutant retained strong expression. Significantly, mRNA for the IL-15 receptor α chain was not expressed in NK cells fromY. pestisKIM5-infected mice as early as day 2 postinfection. These findings suggest that YopM interferes with innate immunity by causing depletion of NK cells, possibly by affecting the expression of IL-15 receptor α and IL-15.
Inbred Strains Derived from Feral Mice Reveal New Pathogenic Mechanisms of Experimental Leishmaniasis Due toLeishmania major
Authors: Babay Besma E. C. , Louzir Hechmi , Kebaïer Chahnaz , Boubaker Samir , Dellagi Koussay , Cazenave Pierre-André 
Published: July 2004

ABSTRACTTwo inbred mouse strains, derived from feral founders, are susceptible to experimental leishmaniasis due toLeishmania majorand support a disease of a severity intermediate between those observed in strains C57BL/6 and BALB/c. Mice of the MAI strain develop a severe, nonhealing, but nonfatal disease with no resistance to a secondary parasite challenge. The immunological responses showed a TH2 dominance characterized by an early peak of interleukin-4 (IL-4) and IL-13. However, neutralization of IL-4, which leads to a resistance phenotype in BALB/c mice, has no effect on disease progression in MAI mice. Mice of strain PWK develop a protracted but self-healing disease, characterized by a mixed TH1-plus-TH2 pattern of immune responses in which IL-10 plays an aggravating role, and acquire resistance to a secondary challenge. These features are close to those observed in human cutaneous leishmaniasis due toL. majorand make PWK mice a suitable model for the human disease.
Gamma Interferon Production by Bovine γδ T Cells following Stimulation with Mycobacterial Mycolylarabinogalactan Peptidoglycan
Authors: Vesosky B. , Turner O. C. , Turner J. , Orme I. M. 
Published: July 2004

ABSTRACTA large percentage of lymphocytes in the blood of cattle express the γδ T-cell receptor, but specific functions for these cells have not yet been clearly defined. There is evidence, however, that human, murine, and bovine γδ T cells have a role in the immune response to mycobacteria. This study investigated the ability of bovine γδ T cells to expand and produce gamma interferon (IFN-γ) in response to stimulation with mycobacterial products. Bovine γδ T cells, isolated from the peripheral blood of healthy cattle, expanded following in vitro stimulation with live mycobacteria, mycobacterial crude cell wall extract, andMycobacterium bovisculture filtrate proteins. In addition, purified γδ T cells, cocultured with purified monocytes and interleukin-2, consistently produced significant amounts of IFN-γ in response to mycobacterial cell wall. The IFN-γ-inducing component of the cell wall was further identified as a proteolytically resistant, non-sodium dodecyl sulfate-soluble component of the mycolylarabinogalactan peptidoglycan.
Multiple Functions of the Leucine-Rich Repeat Protein LrrA of
Treponema denticola
Authors: Ikegami Akihiko , Honma Kiyonobu , Sharma Ashu , Kuramitsu Howard K. 
Published: July 2004

ABSTRACT

The gene
lrrA
, encoding a leucine-rich repeat protein, LrrA, that contains eight consensus tandem repeats of 23 amino acid residues, has been identified in
Treponema denticola
ATCC 35405. A leucine-rich repeat is a generally useful protein-binding motif, and proteins containing this repeat are typically involved in protein-protein interactions. Southern blot analysis demonstrated that
T. denticola
ATCC 35405 expresses the
lrrA
gene, but the gene was not identified in
T. denticola
ATCC 33520. In order to analyze the functions of LrrA in
T. denticola
, an
lrrA
-inactivated mutant of strain ATCC 35405 and an
lrrA
gene expression transformant of strain ATCC 33520 were constructed. Characterization of the mutant and transformant demonstrated that LrrA is associated with the extracytoplasmic fraction of
T. denticola
and expresses multifunctional properties. It was demonstrated that the attachment of strain ATCC 35405 to HEp-2 cell cultures and coaggregation with
Tannerella forsythensis
were attenuated by the
lrrA
mutation. In addition, an in vitro binding assay demonstrated specific binding of LrrA to a portion of the
Tannerella forsythensis
leucine-rich repeat protein, BspA, which is mediated by the N-terminal region of LrrA. It was also observed that the
lrrA
mutation caused a reduction of swarming in
T. denticola
ATCC 35405 and consequently attenuated tissue penetration. These results suggest that the leucine-rich repeat protein LrrA plays a role in the attachment and penetration of human epithelial cells and coaggregation with
Tannerella forsythensis
. These properties may play important roles in the virulence of
T. denticola
.
Mucosally DeliveredSalmonellaLive Vector Vaccines Elicit Potent Immune Responses against a Foreign Antigen in Neonatal Mice Born to Naive and Immune Mothers
Authors: Capozzo Alejandra V. E. , Cuberos Lilian , Levine Myron M. , Pasetti Marcela F. 
Published: July 2004

ABSTRACTThe development of effective vaccines for neonates and very young infants has been impaired by their weak, short-lived, and Th-2 biased responses and by maternal antibodies that interfere with vaccine take. We investigated the ability ofSalmonella entericaserovars Typhi and Typhimurium to mucosally deliver tetanus toxin fragment C (Frag C) as a model antigen in neonatal mice. We hypothesize thatSalmonella, by stimulating innate immunity (contributing to adjuvant effects) and inducing Th-1 cytokines, can enhance neonatal dendritic cell maturation and T-cell activation and thereby prime humoral and cell-mediated immunity. We demonstrate for the first time that intranasal immunization of newborn mice with 109CFU ofS. entericaserovar Typhi CVD 908-htrAandS. entericaserovar Typhimurium SL3261 carrying plasmid pTETlppon days 7 and 22 after birth elicits high titers of Frag C antibodies, previously found to protect against tetanus toxin challenge and similar to those observed in adult mice.Salmonellalive vectors colonized and persisted primarily in nasal tissue. Mice vaccinated as neonates induced Frag C-specific mucosal and systemic immunoglobulin A (IgA)- and IgG-secreting cells, T-cell proliferative responses, and gamma interferon secretion. A mixed Th1- and Th2-type response to Frag C was established 1 week after the boost and was maintained thereafter.S. entericaserovar Typhi carrying pTETlppinduced Frag C-specific antibodies and cell-mediated immunity in the presence of high levels of maternal antibodies. This is the first report that demonstrates the effectiveness ofSalmonellalive vector vaccines in early life.
Role of p38 Mitogen-Activated Protein Kinase in Middle Ear Mucosa Hyperplasia during Bacterial Otitis Media
Authors: Palacios Sean D. , Pak Kwang , Rivkin Alexander Z. , Kayali Ayse G. , Austen Darrell , Aletsee Christoph , Melhus Åsa , Webster Nicholas J. G. , Ryan Allen F. 
Published: July 2004

ABSTRACTHyperplasia of the middle ear mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in middle ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the middle ear mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat middle ear mucosal hyperplasia in which mucosal growth is stimulated by nontypeableHaemophilus influenzaeduring acute otitis media. Hyperplastic mucosal explants treated with the p38α and p38β inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the middle ear mucosa during bacterial otitis media.
In Vitro Models of Tissue Penetration and Destruction by
Porphyromonas gingivalis
Authors: Andrian Elisoa , Grenier Daniel , Rouabhia Mahmoud 
Published: July 2004

ABSTRACT

Porphyromonas gingivalis
is a gram-negative anaerobic bacterium that is considered the key etiologic agent of chronic periodontitis. Arg- and Lys-gingipain cysteine proteinases produced by
P. gingivalis
are key virulence factors and are believed to be essential for significant tissue component degradation, leading to host tissue invasion by periodontopathogens. Two in vitro models were used to determine the extent to which
P. gingivalis
can reach connective tissue. The tissue penetration potential of
P. gingivalis
was first investigated by using an engineered human oral mucosa model composed of normal human epithelial cells and fibroblasts. Internalized bacteria were assessed by transmission electron microscopy. Bacteria were observed within multilayered gingival epithelial cells and in the space between the stratified epithelium and the lamina propria. A gingipain-null mutant strain of
P. gingivalis
was found to be less potent in penetrating tissue than the wild-type strain. Proinflammatory responses to
P. gingivalis
infection were evaluated.
P. gingivalis
increased the secretion of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor alpha. In the second part of the study, the contribution of
P. gingivalis
gingipains to tissue penetration was investigated by using a reconstituted basement membrane model (Matrigel). The penetration of
14
C-labeled
P. gingivalis
cells through Matrigel was significantly reduced when leupeptin, a specific inhibitor of Arg-gingipain activity, was added or when a gingipain-null mutant was used. The results obtained with these two relevant models support the capacities of
P. gingivalis
to infiltrate periodontal tissue and to modulate the proinflammatory response and suggest a critical role of gingipains in tissue destruction.