Showing papers by "Jean-Pierre Gorvel published in 2014"

Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway.

Abstract: 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 (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-β production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies.

Human plasma cells express granzyme B

Abstract: While studying the plasma cell (PC) compartment in human tonsils, we identified that immunoglobulin kappa or lambda chain-expressing PCs are the main cells expressing granzyme B (GrzB). In vitro studies revealed that activated B cells differentiated into GrzB-expressing PCs when co-cultured with macrophages and follicular helper T cells. This effect could be reproduced on combined stimulation of IL-15 (produced by macrophages) and IL-21 (produced by T follicular helper cells) in a STAT3-dependent manner. Whereas IL-21 triggers the transcription of mRNA of GrzB, IL-15 synergizes the translation of GrzB proteins. The precise role of GrzB in PC biology remains to be understood and studies in mice will not help as their PCs do not express GrzB.

Myeloid decidual dendritic cells and immunoregulation of pregnancy: defective responsiveness to Coxiella burnetii and Brucella abortus

Abstract: Dendritic cells (DCs) are a component of the placental immune system, but their role in pregnancy is still poorly understood. Decidual DCs (dDCs) were selected from at-term pregnancy on the basis of CD14 and CD11c expression. A phenotypic analysis revealed that dDCs are characterized by the expression of monocyte-derived DC (moDCs) markers and specific markers such as HLA-G and its ligand ILT4. As demonstrated by whole-genome microarray, dDCs expressed a specific gene program markedly distinct from that of moDCs; it included estrogen- and progesterone-regulated genes and genes encoding immunoregulatory cytokines, which is consistent with the context of foeto-maternal tolerance. A functional analysis of dDCs showed that they were unable to maturate in response to bacterial ligands such as lipopolysaccharide or peptidoglycan, as assessed by the expression of HLA-DR, CD80, CD83 and CD86. When dDCs were incubated with bacteria known for their placenta tropism, Coxiella burnetii and Brucella abortus, they were also unable to maturate and to produce inflammatory cytokines. It is likely that the defective maturation of dDCs and their inability to produce inflammatory cytokines is related to the spontaneous release of IL-10 by these cells. Taken together, these results suggest that dDCs exhibit an immunoregulatory program, which may favor the pathogenicity of C. burnetii or B. abortus.

Innovative Germicidal UV and Photocatalytic System Dedicated to Aircraft Cabin Eliminates Volatile Organic Compounds and Pathogenic Micro-Organisms

Abstract: Air quality on aircraft cabins has become a major public health issue due to the increasing number of air travels since few decades. Exposure to volatile organic compounds (VOC) and micro-organisms is a major concern for human and animal welfare in indoor confinements and especially in aircraft cabins. Here we present an innovative air purification system based on the association of UV-C and photocatalysis. The SAVAB project is aiming at a higher decontamination degree of aircraft cabin air, thus improving health and comfort standards of aircraft crew and passengers. We show a degradation of irritating/noxious VOC such as formaldehyde, toluene, benzene, acetone, which are major pollutants of the aircraft cabins according the NF EN 4618 standard. In the same study, we also demonstrate the inactivation of pathogenic Influenza virus, adenovirus and pathogenic bacteria such as Legionella pneumophila, Burkholderia cepacia, Streptococcus pneumoniae, and Pseudomonas aeruginosa. This innovative system demonstrates its ability to improve air quality in indoor confinements of travel-motorized units such as aircraft cabins and could be applied in hospital environments.

“If you bring an alarm, we will destroy it,” said Brucella to the host cell

Abstract: Pathogenic brucellae are the agent of brucellosis, a disease that causes abortion and infertility in natural hosts such as sheep, goats, or cattle. Brucella melitensis, Brucella abortus, and Brucel...