Interleukin-10 stimulates Coxiella burnetii replication in human monocytes through tumor necrosis factor down-modulation: role in microbicidal defect of Q fever.
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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 beta1 had no effect on bacterial replication. C. burnetii replication involves the down-modulation of tumor necrosis factor (TNF) release. First, interleukin-10 suppressed C. 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. (+info)
Activation of protein tyrosine kinases by Coxiella burnetii: role in actin cytoskeleton reorganization and bacterial phagocytosis.
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Coxiella burnetii, the agent of Q fever, is an obligate intracellular microorganism that grows in monocytes/macrophages. The internalization of virulent organisms by monocytes is lower than that of avirulent variants and is associated with actin cytoskeleton reorganization. We studied the activation of protein tyrosine kinases (PTKs) by C. burnetii in THP-1 monocytes. Virulent organisms induced early PTK activation and the tyrosine phosphorylation of several endogenous substrates, including Hck and Lyn, two Src-related kinases. PTK activation reflects C. burnetii virulence since avirulent variants were unable to stimulate PTK. We also investigated the role of PTK activation in C. burnetii-stimulated F-actin reorganization. Tyrosine-phosphorylated proteins were colocalized with F-actin inside cell protrusions induced by C. burnetii, and PTK activity was increased in Triton X-100-insoluble fractions. In addition, lavendustin A, a PTK inhibitor, and PP1, a Src kinase inhibitor, prevented C. burnetii-induced cell protrusions and F-actin reorganization. We finally assessed the role of PTK activation in bacterial phagocytosis. Pretreatment of THP-1 cells with lavendustin A and PP1 upregulated the uptake of virulent C. burnetii but had no effect on the phagocytosis of avirulent organisms. Thus, it is likely that PTK activation by C. burnetii negatively regulates bacterial uptake by interfering with cytoskeleton organization. (+info)
Myocarditis, a rare but severe manifestation of Q fever: report of 8 cases and review of the literature.
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Myocarditis has only rarely been described as a manifestation of acute Q fever. Among our series of 1276 patients in whom acute Q fever was diagnosed during 1985--1999, myocarditis was diagnosed in 8. Two patients (25.0%) developed cardiac symptoms during the course of interstitial pneumonia, 2 (25.0%) initially presented with unexplained fever, and 1 (12.5%) presented with febrile cutaneous rash. In 3 patients, cardiac symptoms were inaugural: 1 patient experienced heart failure, and 2 experienced precordial pain. Dilated cardiomyopathy was documented in 7 patients, and 2 (1 of whom had undergone heart transplantation) died despite therapy. In addition, 1 patient was scheduled for heart transplantation because of cardiac insufficiency. When the patients in this study were compared with 32 control patients with acute Q fever, no specific epidemiological or clinical features were associated with this disease except worse prognosis (P=.006). Moreover, among the 12 patients from our series who died as a result of acute Q fever, 2 patients, who were significantly younger than the other 9 patients (P=.03), had myocarditis. Our study highlights the severity of Coxiella burnetii myocarditis. (+info)
Q fever during pregnancy: an emerging cause of prematurity and abortion.
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BACKGROUND: Although the pathogenic role of Coxiella burnetii infection during pregnancy is controversial, some cases of stillbirth and abortion occurring after an acute or chronic infection have been mentioned in the literature. Recently, Q fever has been advocated as a significant cause of morbidity and mortality in pregnancy CASE: We describe an 18-year-old primipara woman admitted to our hospital for high fever and pancytopenia during an acute C. burnetii infection. She was successfully treated with clarithromycin, overcoming fever and pancytopenia. Finally, she gave birth to a healthy infant, and 1 year later both remained well. CONCLUSION: Q fever is a potentially serious disease in pregnancy owing to the possibility of placenta infection and fetal transmission affecting its outcome. Q fever infection should be suspected in unexplained febrile episodes or abortion during pregnancy, when epidemiologic and clinical data are present. We believe that C. burnetii serology should be tested in cases of fever of known origin or unexplained abortions, as the TORCH infections are. (+info)
Sexually transmitted Q fever.
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We report the sexual transmission of Coxiella burnetii from a man with occupationally acquired Q fever to his wife. Fifteen days after coitus, his wife also developed serologically proven acute Q fever. C. burnetii DNA sequences were detected by polymerase chain reaction (PCR) performed on semen samples obtained from the husband at 4 and 15 months after the onset of acute Q fever, but PCR results were variable at 23 months, indicating the presence of few organisms. (+info)
Suburban transmission of Q fever in French Guiana: evidence of a wild reservoir.
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The annual incidence of Q fever in French Guiana was found to have increased in 1996 and was 37/100,000 population over the last 4 years. Subsequent investigations in Cayenne and its suburbs indicated that a wild reservoir of the bacteria was responsible for the epidemiologic pattern. A case-control study showed that residence near a forest and occupations and activities that result in exposure to aerosols of dusts from the soil are risk factors for Q fever. By means of time-series analysis, a strong positive correlation between rainfall and the incidence of Q fever with a time lag of 1-3 months was found. The spatial distribution of the cases showed that transmission occurs widely throughout greater Cayenne, which is incompatible with a pinpoint source of contamination. Transmission from livestock and dissemination of the bacteria by the wind appeared to be unlikely, which strengthens the hypothesis that a wild reservoir is responsible for transmission. (+info)
Characterization of a stress-induced alternate sigma factor, RpoS, of Coxiella burnetii and its expression during the development cycle.
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Coxiella burnetii is an obligate intracellular bacterium that resides in an acidified phagolysosome and has a remarkable ability to persist in the extracellular environment. C. burnetii has evolved a developmental cycle that includes at least two morphologic forms, designated large cell variants (LCV) and small cell variants (SCV). Based on differential protein expression, distinct ultrastructures, and different metabolic activities, we speculated that LCV and SCV are similar to typical logarithmic- and stationary-phase growth stages. We hypothesized that the alternate sigma factor, RpoS, a global regulator of genes expressed under stationary-phase, starvation, and stress conditions in many bacteria, regulates differential expression in life cycle variants of C. burnetii. To test this hypothesis, we cloned and characterized the major sigma factor, encoded by an rpoD homologue, and the stress response sigma factor, encoded by an rpoS homologue. The rpoS gene was cloned by complementation of an Escherichia coli rpoS null mutant containing an RpoS-dependent lacZ fusion (osmY::lacZ). Expression of C. burnetii rpoS was regulated by growth phase in E. coli (induced upon entry into stationary phase). A glutathione S-transferase-RpoS fusion protein was used to develop polyclonal antiserum against C. burnetii RpoS. Western blot analysis detected abundant RpoS in LCV but not in SCV. These results suggest that LCV and SCV are not comparable to logarithmic and stationary phases of growth and may represent a novel adaptation for survival in both the phagolysosome and the extracellular environment. (+info)
Atypical manifestations of chronic Q fever.
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Chronic Q fever is uncommon, with the majority of cases manifesting as culture-negative endocarditis. In this report, we describe 3 patients who present with atypical manifestations of chronic Q fever. These were a 43-year-old man whose site of chronic Q fever was the central nervous system, a 53-year-old woman who underwent coronary angioplasty 6 days before the onset of symptoms of acute Q fever and within 4 months had serologic evidence consistent with chronic Q fever, and a 66-year-old man with fever of unknown origin, a pancreatic mass, and aorto-bifemoral grafts. (+info)