scholarly journals Role for the CD28 Molecule in the Control of Coxiella burnetii Infection

2006 ◽  
Vol 74 (3) ◽  
pp. 1800-1808 ◽  
Author(s):  
Amélie Honstettre ◽  
Soraya Meghari ◽  
Jacques A. Nunès ◽  
Hubert Lepidi ◽  
Didier Raoult ◽  
...  
Keyword(s):  
Coxiella Burnetii ◽  
Q Fever ◽  
Interleukin 10 ◽  
Peritoneal Macrophages ◽  
Granuloma Formation ◽  
Microbial Pathogens ◽  
Cell Mediated Immunity ◽  
Obligate Intracellular ◽  
Cell Mediated Immune Response ◽  
Necrosis Factor

ABSTRACT Q fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular bacterium that replicates in macrophages. As cell-mediated immune response to microbial pathogens requires signals mediated by T-cell receptors and costimulatory molecules such as CD28, we wondered if CD28 is involved in protection against C. burnetii infection. CD28-deficient (CD28−/−) mice were inoculated with C. burnetii by intraperitoneal and intravenous routes. With both wild-type and CD28−/− mice, C. burnetii organisms were detected exclusively in spleen and liver. The antibody response against C. burnetii was impaired in CD28−/− animals, but, surprisingly, the lack of CD28 decreased C. burnetii burden in the infected tissues, whatever the manner of inoculation of bacteria. The CD28 deficiency had no effect on either granuloma formation, which reflects cell-mediated immunity against C. burnetii, or the production of gamma interferon and tumor necrosis factor, two cytokines known to be involved in granuloma formation. On the other hand, the production of interleukin-10 (IL-10) by peritoneal macrophages was highly impaired in CD28−/− mice. The results suggest that CD28 initiates a signal that favors C. burnetii replication through the modulation of the IL-10 pathway.

scholarly journals Phagocytosis of Apoptotic Cells Increases the Susceptibility of Macrophages to Infection with Coxiella burnetii Phase II through Down-Modulation of Nitric Oxide Production

2004 ◽  
Vol 72 (4) ◽  
pp. 2075-2080 ◽  
Author(s):  
Dario S. Zamboni ◽  
Michel Rabinovitch
Keyword(s):  
Nitric Oxide ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Bacterial Load ◽  
Peritoneal Macrophages ◽  
No Synthase ◽  
Obligate Intracellular Bacterium ◽  
Biologically Relevant ◽  
Obligate Intracellular ◽  
Synthase Inhibitor

ABSTRACT Coxiella burnetii, the agent of Q fever in humans and coxiellosis in other mammals, is an obligate intracellular bacterium which is sheltered and multiplies within typically large phagolysosome-like replicative vacuoles (LRVs). We have previously shown that, compared with fibroblasts, mouse resident peritoneal macrophages control the development of LRVs and bacterial multiplication within these vacuoles. Earlier experiments with the nitric oxide (NO) synthase inhibitor aminoguanidine (AG) revealed that the control is exerted by NO induced by the bacteria. We report here that phagocytosis of apoptotic-like, but not of aldehyde-killed, lymphocytes by the macrophages reduced the production of NO induced by the bacteria and increased the development of LRVs and, therefore, the total bacterial load in the cultures. Experiments with macrophages from mice deficient for inducible NO synthase (iNOS−/−) confirmed the involvement of NO in the control of infection, since neither apoptotic lymphocytes nor AG affected the development of LRVs in these phagocytes. Since macrophages are important for the clearance of apoptotic bodies and C. burnetii is able to induce apoptosis in human monocytes, the phenomenon shown here may be biologically relevant to the development of Q fever and coxiellosis.

A study of the correlation between Coxiella burnetii seropositivity and abortions in sheep in Eastern and Southeastern Turkey

2016 ◽  
Author(s):  
Ayse Kilic ◽  
Hakan Kalender
Keyword(s):  
Immunosorbent Assay ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Eastern Anatolia ◽  
Obligate Intracellular Bacterium ◽  
Serum Samples ◽  
Obligate Intracellular ◽  
Elisa Kit

Q fever is a zoonotic disease that occurs worldwide and is caused by the obligate intracellular bacterium Coxiella burnetii. Infected animals are usually asymptomatic, but infection can cause abortion and stillbirth in ruminants. The main purpose of this study was to evaluate prevalance of Coxiella burnetii infection in aborted and nonaborted sheep serum samples in Eastern Anatolia region by using enzyme-linked immunosorbent assay (ELISA). The determine of prevalance in sheep flocks from four provinces (Elazig, Malatya, Tunceli, Bitlis) and tested for anti-C.burnetii antibody detection, by means of Chekit Q fever Elisa kit. 350 serum samples obtained from flocks belonging aborted sheep showed that a total of 56 (16%) were detected seropositivity, whereas 171 serum samples obtained from nonaborted sheep flocks in 13 of the 171 (7.60%) for C.burnetii in seropositivity were observed. Coxiellosis should be considered an important cause of sheep with abortion history and nonaborted in Elazig and neighboring provinces.

scholarly journals Serological characterization of surface-exposed proteins of Coxiella burnetii

Microbiology ◽  
2014 ◽  
Vol 160 (12) ◽  
pp. 2718-2731 ◽  
Author(s):  
Jun Jiao ◽  
Xiaolu Xiong ◽  
Yong Qi ◽  
Wenping Gong ◽  
Changsong Duan ◽  
...  
Keyword(s):  
Coxiella Burnetii ◽  
Bioinformatics Analysis ◽  
Q Fever ◽  
Obligate Intracellular ◽  
Rickettsia Rickettsii ◽  
Serological Characterization ◽  
Vaccine Antigens ◽  
Mycoplasma Pneumonia ◽  
Dimensional Electrophoresis

The obligate intracellular Gram-negative bacterium Coxiella burnetii causes Q fever, a worldwide zoonosis. Here we labelled Cox . burnetii with biotin and used biotin-streptavidin affinity chromatography to isolate surface-exposed proteins (SEPs). Using two-dimensional electrophoresis combined with mass spectrometry, we identified 37 proteins through bioinformatics analysis. Thirty SEPs expressed in Escherichia coli (recombinant SEPs, rSEPs) were used to generate microarrays, which were probed with sera from mice experimentally infected with Cox. burnetii or sera from Q fever patients. Thirteen rSEPs were recognized as seroreactive, and the majority reacted with at least 50 % of the sera from mice infected with Cox. burnetii but not with sera from mice infected with Rickettsia rickettsii, R. heilongjiangensis, or R. typhi. Further, 13 proteins that reacted with sera from patients with Q fever did not react with sera from patients with brucellosis or mycoplasma pneumonia. Our results suggest that these seroreactive SEPs have potential as serodiagnostic antigens or as subunit vaccine antigens against Q fever.

scholarly journals Macrophage deactivation by interleukin 10.

1991 ◽  
Vol 174 (6) ◽  
pp. 1549-1555 ◽  
Author(s):  
C Bogdan ◽  
Y Vodovotz ◽  
C Nathan
Keyword(s):  
Transforming Growth Factor Beta ◽  
Neutralizing Antibodies ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Peritoneal Macrophages ◽  
Microbial Pathogens ◽  
Tnf Alpha ◽  
Lymphocyte Function ◽  
Oxygen Intermediates ◽  
Necrosis Factor Alpha

Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes. m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi. IL-10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently.

scholarly journals Dysregulation of Cytokines in Acute Q Fever: Role of Interleukin‐10 and Tumor Necrosis Factor in Chronic Evolution of Q Fever

2003 ◽  
Vol 187 (6) ◽  
pp. 956-962 ◽  
Author(s):  
Amélie Honstettre ◽  
Guenièvre Imbert ◽  
Eric Ghigo ◽  
Frédérique Gouriet ◽  
Christian Capo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Q Fever ◽  
Interleukin 10 ◽  
Acute Q Fever ◽  
Necrosis Factor

scholarly journals αvβ3 Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes

2000 ◽  
Vol 68 (10) ◽  
pp. 5673-5678 ◽  
Author(s):  
Jérôme Dellacasagrande ◽  
Eric Ghigo ◽  
Sarah Machergui-El ◽  
Hammami ◽  
Rudolf Toman ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Coxiella Burnetii ◽  
Tumor Necrosis ◽  
Q Fever ◽  
Polymyxin B ◽  
Bacterial Lipopolysaccharide ◽  
Host Cells ◽  
Αvβ3 Integrin ◽  
Human Monocytes ◽  
Necrosis Factor

ABSTRACT Coxiella burnetii, the agent of Q fever, enters human monocytes through αvβ3 integrin and survives inside host cells. In addition, C. burnetiistimulates the synthesis of inflammatory cytokines including tumor necrosis factor (TNF) by monocytes. We studied the role of the interaction of C. burnetii with THP-1 monocytes in TNF production. TNF transcripts and TNF release reached maximum values within 4 h. Almost all monocytes bound C. burnetiiafter 4 h, while the percentage of phagocytosing monocytes did not exceed 20%. Cytochalasin D, which prevented the uptake of C. burnetii without interfering with its binding, did not affect the expression of TNF mRNA. Thus, bacterial adherence, but not phagocytosis, is necessary for TNF production by monocytes. The monocyte αvβ3 integrin was involved in TNF synthesis since peptides containing RGD sequences and blocking antibodies against αvβ3 integrin inhibited TNF transcripts induced by C. burnetii. Nevertheless, the cross-linking of αvβ3 integrin by specific antibodies was not sufficient to induce TNF synthesis. The signal delivered by C. burnetii was triggered by bacterial lipopolysaccharide (LPS). Polymyxin B inhibited the TNF production stimulated by C. burnetii, and soluble LPS isolated fromC. burnetii largely mimicked viable bacteria. On the other hand, avirulent variants of C. burnetii induced TNF production through an increased binding to monocytes rather than through the potency of their LPS. We suggest that the adherence ofC. burnetii to monocytes via αvβ3 integrin enables surface LPS to stimulate TNF production in THP-1 monocytes.

scholarly journals Q fever

2012 ◽  
Vol 33 (4) ◽  
pp. 170
Author(s):  
Robert Norton
Keyword(s):  
Coxiella Burnetii ◽  
Q Fever ◽  
Environmental Sampling ◽  
High Likelihood ◽  
Obligate Intracellular Bacterium ◽  
Wet Season ◽  
Obligate Intracellular ◽  
Chronic Q Fever ◽  
Specific Symptoms ◽  
Occupational Contact

Q fever is a zoonosis caused by the obligate intracellular bacterium Coxiella burnetii. North Queensland has some of the highest rates of Q fever notifications in Australia. The clinical diagnosis of Q fever can be difficult with non-specific symptoms. Up to 5% of cases will develop chronic Q fever with a high likelihood of endocarditis. Diagnosis is essentially by serology. In North Queensland cases have clustered in relatively new, semi-rural suburbs which lie adjacent to native bushland. Native mammals are attracted to new growth in these cleared areas, particularly after the wet season. There is little or no occupational contact with traditional sources of Q fever such as cattle. Seroprevalence studies on native mammals have shown higher levels of seropositivity in native mammals than in cattle. It is postulated that the increase in human cases seen from these areas are a direct effect of interaction between native mammals and humans. Further studies on environmental sampling is currently under way.

scholarly journals Vaccine-induced protective immunity against coxiella burnetii

2019 ◽  
Author(s):  
◽  
Lindsey Elizabeth Ledbetter
Keyword(s):  
T Cells ◽  
Coxiella Burnetii ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Q Fever ◽  
Therapeutic Vaccine ◽  
T Cell Subsets ◽  
Cell Mediated Immunity ◽  
Vaccine Protection ◽  
Vaccine Immunity

Coxiella burnetii is an obligate intracellular Gram-negative bacterial pathogen and the causative agent of human Q fever. This disease presents acutely as a flu-like illness, although it can escalate to a chronic and often fatal disease when left untreated. Considering no FDA-approved vaccine exists, the creation of a safe and effective vaccine remains an important public health goal. A formalin-inactivated C. burnetii Nine Mile strain phase I whole-cell vaccine generates protective immunity in a mouse model of experimental Q fever, although the mechanisms of protection remain unclear. Chapter 3 details my work establishing an early vaccine protection model and elucidating the cellular immune response which elicits early protection. The early time point at which PIV protects has implications for its use as a therapeutic vaccine. Furthermore, the innate-driven mechanisms by which it protects can be exploited for an improved Q fever vaccine. The importance of T cells in vaccine immunity against C. burnetii is well supported, however, multiple questions remain. It is unclear how CD4+ or CD8+ T cells contribute to vaccine protection, and the role of specific CD4+ T cell subsets is unknown. IFN-[theta] is critical for primary defense against C. burnetii, though its importance in vaccine immunity is undetermined. Chapter 4 describes my work aimed at filling these knowledge gaps. Vaccine development efforts have largely focused on the generation of antibodies as a correlate of protection. It has become clear that targeting T cells is more critical to vaccine protection and a better understanding of the mechanisms of cell-mediated immunity will inform future Q fever vaccine development.

scholarly journals Interleukin-10 Stimulates Coxiella burnetiiReplication in Human Monocytes through Tumor Necrosis Factor Down-Modulation: Role in Microbicidal Defect of Q Fever

2001 ◽  
Vol 69 (4) ◽  
pp. 2345-2352 ◽  
Author(s):  
Eric Ghigo ◽  
Christian Capo ◽  
Didier Raoult ◽  
Jean-Louis Mege
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Q Fever ◽  
Interleukin 10 ◽  
Transforming Growth Factor Β1 ◽  
Bacterial Killing ◽  
Chronic Q Fever ◽  
Bacterial Replication ◽  
Necrosis Factor

ABSTRACT Coxiella burnetii, an obligate intracellular bacterium, is the agent of Q fever. The chronic form of the disease is associated with the overproduction of interleukin-10 and deficient C. burnetii killing by monocytes. We hypothesized that the replication of C. burnetii inside monocytes requires a macrophage-deactivating cytokine such as interleukin-10. In the absence of interleukin-10, C. burnetii survived but did not replicate in monocytes. C. burnetii replication (measured 15 days) was induced in interleukin-10-treated monocytes. This effect of interleukin-10 is specific since transforming growth factor β1 had no effect on bacterial replication. C. burnetii replication involves the down-modulation of tumor necrosis factor (TNF) release. First, interleukin-10 suppressedC. burnetii-stimulated production of TNF. Second, the addition of recombinant TNF to interleukin-10-treated monocytes inhibited bacterial replication. Third, the incubation of infected monocytes with neutralizing anti-TNF antibodies favored C. burnetii replication. On the other hand, deficient C. burnetii killing by monocytes from patients with chronic Q fever involves interleukin-10. Indeed, C. burnetii replication was observed in monocytes from patients with Q fever endocarditis, but not in those from patients with acute Q fever. Bacterial replication was inhibited by neutralizing anti-interleukin-10 antibodies. As monocytes from patients with endocarditis overproduced interleukin-10, the defective bacterial killing is likely related to endogenous interleukin-10. These results suggest that interleukin-10 enables monocytes to support C. burnetii replication and to favor the development of chronic Q fever.

scholarly journals Coxiella burnetii Inhibits Activation of Host Cell Apoptosis through a Mechanism That Involves Preventing Cytochrome c Release from Mitochondria

2007 ◽  
Vol 75 (11) ◽  
pp. 5282-5289 ◽  
Author(s):  
Anja Lührmann ◽  
Craig R. Roy
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Coxiella Burnetii ◽  
Mammalian Cells ◽  
Q Fever ◽  
Host Cells ◽  
Intracellular Pathogen ◽  
Obligate Intracellular ◽  
Cell Death Pathway ◽  
Obligate Intracellular Pathogen

ABSTRACT Coxiella burnetii is an obligate intracellular pathogen and the etiological agent of the human disease Q fever. C. burnetii infects mammalian cells and then remodels the membrane-bound compartment in which it resides into a unique lysosome-derived organelle that supports bacterial multiplication. To gain insight into the mechanisms by which C. burnetii is able to multiply intracellularly, we examined the ability of host cells to respond to signals that normally induce apoptosis. Our data show that mammalian cells infected with C. burnetii are resistant to apoptosis induced by staurosporine and UV light. C. burnetii infection prevented caspase 3/7 activation and limited fragmentation of the host cell nucleus in response to agonists that induce apoptosis. Inhibition of bacterial protein synthesis reduced the antiapoptotic effect that C. burnetii exerted on infected host cells. Inhibition of apoptosis in C. burnetii-infected cells did not correlate with the degradation of proapoptotic BH3-only proteins involved in activation of the intrinsic cell death pathway; however, cytochrome c release from mitochondria was diminished in cells infected with C. burnetii upon induction of apoptosis. These data indicate that C. burnetii can interfere with the intrinsic cell death pathway during infection by producing proteins that either directly or indirectly prevent release of cytochrome c from mitochondria. It is likely that inhibition of apoptosis by C. burnetii represents an important virulence property that allows this obligate intracellular pathogen to maintain host cell viability despite inducing stress that would normally activate the intrinsic death pathway.

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