Modulation of the immune response by the type-III secretion system.

is an opportunistic pathogen that can cause critical cellular damage and subvert the immune response to promote its survival. Among the numerous virulence factors of , the type III secretion system (T3SS) is involved in host cell pathogenicity. Using a needle-like structure, T3SS detects eukaryotic cells and injects toxins directly into their cytosol, thus highlighting its ability to interfere with the host immune response.

Role of Host and Bacterial Lipids in Respiratory Infections.

The opportunistic pathogen is one of the most common agents of respiratory infections and has been associated with high morbidity and mortality rates. The ability of to cause severe respiratory infections results from the coordinated action of a variety of virulence factors that promote bacterial persistence in the lungs. Several of these virulence mechanisms are mediated by bacterial lipids, mainly lipopolysaccharide, rhamnolipid, and outer membrane vesicles.

Insights of OxyR role in mechanisms of host-pathogen interaction of Corynebacterium diphtheriae.

Corynebacterium diphtheriae, the leading causing agent of diphtheria, has been increasingly related to invasive diseases, including sepsis, endocarditis, pneumonia, and osteomyelitis. Oxidative stress defense is required not only for successful growth and survival under environmental conditions but also in the regulation of virulence mechanisms of human pathogenic species, by promoting mucosal colonization, survival, dissemination, and defense against the innate immune system. OxyR, functioning as a negative and/or positive transcriptional regulator, has been included among the major bacterial coordinators of antioxidant response.

Reactive oxygen species generation mediated by NADPH oxidase and PI3K/Akt pathways contribute to invasion of Streptococcus agalactiae in human endothelial cells.

BACKGROUND Streptococcus agalactiae can causes sepsis, pneumonia, and meningitis in neonates, the elderly, and immunocompromised patients. Although the virulence properties of S. agalactiae have been partially elucidated, the molecular mechanisms related to reactive oxygen species (ROS) generation in infected human endothelial cells need further investigation.

Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis.

parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive and mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of (skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in infection .

HIV-1 Tat protein enhances the intracellular growth of Leishmania amazonensis via the ds-RNA induced protein PKR.

HIV-1 co-infection with human parasitic diseases is a growing public health problem worldwide. Leishmania parasites infect and replicate inside macrophages, thereby subverting host signaling pathways, including the response mediated by PKR. The HIV-1 Tat protein interacts with PKR and plays a pivotal role in HIV-1 replication.

The human parasite Leishmania amazonensis downregulates iNOS expression via NF-κB p50/p50 homodimer: role of the PI3K/Akt pathway.

Leishmania amazonensis activates the NF-κB transcriptional repressor homodimer (p50/p50) and promotes nitric oxide synthase (iNOS) downregulation. We investigated the role of PI3K/Akt in p50/p50 NF-κB activation and the effect on iNOS expression in L. amazonensis infection.

Contribution of the platelet activating factor signaling pathway to cerebral microcirculatory dysfunction during experimental sepsis by ExoU producing Pseudomonas aeruginosa.

Intravital microscopy was used to assess the involvement of ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, in dysfunction of cerebral microcirculation during experimental pneumosepsis. Cortical vessels from mice intratracheally infected with low density of the ExoU-producing PA103 P. aeruginosa strain exhibited increased leukocyte rolling and adhesion to venule endothelium, decreased capillar density and impaired arteriolar response to vasoactive acetylcholine.

ExoU-induced redox imbalance and oxidative stress in airway epithelial cells during Pseudomonas aeruginosa pneumosepsis.

ExoU is a potent proinflammatory toxin produced by Pseudomonas aeruginosa, a major agent of severe lung infection and sepsis. Because inflammation is usually associated with oxidative stress, we investigated the effect of ExoU on free radical production and antioxidant defense mechanisms during the course of P. aeruginosa infection.

Central role of PAFR signalling in ExoU-induced NF-κB activation.

ExoU is an important virulence factor in acute Pseudomonas aeruginosa infections. Here, we unveiled the mechanisms of ExoU-driven NF-κB activation by using human airway cells and mice infected with P. aeruginosa strains.

The infection of microvascular endothelial cells with ExoU-producing Pseudomonas aeruginosa triggers the release of von Willebrand factor and platelet adhesion.

An increased plasma concentration of von Willebrand factor (vWF) is detected in individuals with many infectious diseases and is accepted as a marker of endothelium activation and prothrombotic condition. To determine whether ExoU, a Pseudomonas aeruginosa cytotoxin with proinflammatory activity, enhances the release of vWF, microvascular endothelial cells were infected with the ExoU-producing PA103 P. aeruginosa strain or an exoU-deficient mutant.

ExoU activates NF-κB and increases IL-8/KC secretion during Pseudomonas aeruginosa infection.

ExoU, a Pseudomonas aeruginosa cytotoxin injected into host cytosol by type III secretion system, exhibits a potent proinflammatory activity that leads to a marked recruitment of neutrophils to infected tissues. To evaluate the mechanisms that account for neutrophil infiltration, we investigated the effect of ExoU on IL-8 secretion and NF-κB activation. We demonstrate that ExoU increases IL-8 mRNA and protein levels in P.

ExoU modulates soluble and membrane-bound ICAM-1 in Pseudomonas aeruginosa-infected endothelial cells.

ExoU, a Pseudomonas aeruginosa cytotoxin injected via the type III secretion system into host cells, possesses eicosanoid-mediated proinflammatory properties due to its phospholipase A(2) (PLA(2)) activity. This report addressed the question whether ExoU may modulate the expression of adhesion molecules in host cells, therefore contributing to the recruitment of leukocyte into infected tissues. ExoU was shown to down-regulate membrane-bound ICAM-1 (mICAM-1) and up-regulate the release of soluble ICAM-1 (sICAM-1) from P.

Type III secretion-mediated killing of endothelial cells by Pseudomonas aeruginosa.

Pseudomonas aeruginosa, a common agent of septicemia, enters into human endothelial cellsin vitro but the effects of bacterial infection have not been addressed properly. In this study, human umbilical vein endothelial cells (HUVEC) were infected by the noninvasive PA103 and the invasive PAO1 P. aeruginosa strains and the viability of infected cells was assessed by the methyltiazole tetrazolium (MTT) assay.