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Imbalance of Circulating Monocyte Subsets and PD-1 Dysregulation in Q Fever Endocarditis: The Role of IL-10 in PD-1 Modulation

Q fever endocarditis, a severe complication of Q fever, is associated with a defective immune response, the mechanisms of which are poorly understood. We hypothesized that Q fever immune deficiency is related to altered distribution and activation of circulating monocyte subsets. Monocyte subsets were analyzed by flow cytometry in peripheral blood mononuclear cells from patients...

Monocyte Responses in the Context of Q Fever: From a Static Polarized Model to a Kinetic Model of Activation

Christian Capo 0 Jean-Louis Mege 0 0 Aix-Marseille University , URMITE, CNRS UMR 7278, IRD 198, INSERM 1095, Marseille , France Background. Q fever is caused by Coxiella burnetii, a bacterium that persists

Intracellular Bacteria Interfere with Dendritic Cell Functions: Role of the Type I Interferon Pathway

Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs...

Overexpression of the Per2 Gene in Male Patients with Acute Q Fever

The prevalence of Q fever is higher in men than in women. Because the expression of circadian clock genes differs in male and female mice infected with Coxiella burnetii, we hypothesized that circadian genes are differently modulated in men and women with Q fever. The expression of the Per2 gene was significantly (P = .01) increased in males with acute Q fever compared with...

Persistence of Coxiella burnetii, the Agent of Q Fever, in Murine Adipose Tissue

Coxiella burnetii, the agent of Q fever, is known to persist in humans and rodents but its cellular reservoir in hosts remains undetermined. We hypothesized that adipose tissue serves as a C. burnetii reservoir during bacterial latency. BALB/c and C57BL/6 mice were infected with C. burnetii by the intraperitoneal route or the intracheal route. Adipose tissue was tested for the...

Defective Monocyte Dynamics in Q Fever Granuloma Deficiency

Background. The outcome of Q fever, an infectious disease caused by Coxiella burnetii, is associated with granuloma formation. Granulomas are present in patients with resolutive Q fever but are lacking in patients with chronic Q fever. Methods. Study of granuloma formation requires invasive approaches. Here, we took advantage of a recently described method that enables in vitro...

The Gene Expression Analysis of Blood Reveals S100A11 and AQP9 as Potential Biomarkers of Infective Endocarditis

Background The diagnostic and prognostic assessments of infective endocarditis (IE) are challenging. To investigate the host response during IE and to identify potential biomarkers, we determined the circulating gene expression profile using whole genome microarray analysis. Methods and Results A transcriptomic case-control study was performed on blood samples from patients with...

Global Analysis of Circulating Immune Cells by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry

Background MALDI-TOF mass spectrometry is currently used in microbiological diagnosis to characterize bacterial populations. Our aim was to determine whether this technique could be applied to intact eukaryotic cells, and in particular, to cells involved in the immune response. Methodology/Principal Findings A comparison of frozen monocytes, T lymphocytes and polymorphonuclear...

Sex-Related Differences in Gene Expression Following Coxiella burnetii Infection in Mice: Potential Role of Circadian Rhythm

Background Q fever, a zoonosis due to Coxiella burnetii infection, exhibits sexual dimorphism; men are affected more frequently and severely than women for a given exposure. Here we explore whether the severity of C. burnetii infection in mice is related to differences in male and female gene expression profiles. Methodology/Principal Findings Mice were infected with C. burnetii...

Infection of Endothelial Cells with Virulent Rickettsia prowazekii Increases the Transmigration of Leukocytes

Rickettsia prowazekii, the etiologic agent of epidemic typhus, infects vascular endothelium, leading to vasculitis and tissue infiltration of leukocytes. Murine and human endothelial cells (ECs) were infected with R. prowazekii, including the virulent Breinl strain and the attenuated Madrid E strain. The transendothelial migration (TM) of murine and human peripheral blood...

Adipose Tissue Serves as a Reservoir for Recrudescent Rickettsia prowazekii Infection in a Mouse Model

Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice...

IL-16 Promotes T. whipplei Replication by Inhibiting Phagosome Conversion and Modulating Macrophage Activation

The replication of Tropheryma whipplei (the agent of Whipple's disease) within human macrophages is associated with the expression of IL-16, a cytokine known for its chemotactic and inflammatory properties. In this study, we asked whether IL-16 acts on T. whipplei replication by interfering with the endocytic pathway. We observed that in macrophages, T. whipplei was located...

Deficient Transendothelial Migration of Leukocytes in Q Fever: The Role Played by Interleukin-10

, Christian Capo, Didier Raoult, and Jean-Louis Mege Unite des Rickettsies, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 6020, Universite de la Me diterrane e, Institut Fe de ratif

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

Orientia tsutsugamushi is the causal agent of scrub typhus, a public health problem in the Asia-Pacific region and a life-threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushi altered the...

Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis

Mimivirus, or Acanthamoeba polyphaga mimivirus (APMV), a giant double-stranded DNA virus that grows in amoeba, was identified for the first time in 2003. Entry by phagocytosis within amoeba has been suggested but not demonstrated. We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive APMV replication. Clathrin- and...

The Uptake of Apoptotic Cells Drives Coxiella burnetii Replication and Macrophage Polarization: A Model for Q Fever Endocarditis

Patients with valvulopathy have the highest risk to develop infective endocarditis (IE), although the relationship between valvulopathy and IE is not clearly understood. Q fever endocarditis, an IE due to Coxiella burnetii, is accompanied by immune impairment. Patients with valvulopathy exhibited increased levels of circulating apoptotic leukocytes, as determined by the...

Coxiella burnetii, the Agent of Q Fever, Replicates within Trophoblasts and Induces a Unique Transcriptional Response

Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium typically found in myeloid cells. The infection is a source of severe obstetrical complications in humans and cattle and can undergo chronic evolution in a minority of pregnant women. Because C. burnetii is found in the placentas of aborted fetuses, we investigated the possibility that it could...

Persistent Coxiella burnetii Infection in Mice Overexpressing IL-10: An Efficient Model for Chronic Q Fever Pathogenesis

Interleukin (IL)-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL...

The Transcriptional Programme of Human Heart Valves Reveals the Natural History of Infective Endocarditis

Infective endocarditis (IE) is an infectious disease that is mainly caused by Staphylococcus aureus and Streptococcus sp. It usually leads to valvular destruction and vegetation formation. Its pathophysiology is badly understood and likely involves immune and coagulation systems with close interactions with the microorganism. Our objective was to evaluate host response by...

New Microbicidal Functions of Tracheal Glands: Defective Anti-Infectious Response to Pseudomonas aeruginosa in Cystic Fibrosis

Tracheal glands (TG) may play a specific role in the pathogenesis of cystic fibrosis (CF), a disease due to mutations in the cftr gene and characterized by airway inflammation and Pseudomonas aeruginosa infection. We compared the gene expression of wild-type TG cells and TG cells with the cftr ΔF508 mutation (CF-TG cells) using microarrays covering the whole human genome. In the...