Chlamydia trachomatis is one of the most common bacterial pathogens and etiological agent debilitating sexually transmitted ocular diseases in humans. The organism an obligate intracellular prokaryote characterized by a highly specialized biphasic developmental cycle. We have performed genomic transcriptional analysis chlamydial This approach has led to identification small subset genes that control primary (immediate-early genes) secondary (late differentiation stages Immediate-early gene...

Background. Nosocomial infections with Klebsiella pneumoniae are a frequent cause of Gram-negative bacterial sepsis. To understand the functioning host innate immune components in this disorder, we examined previously uninvestigated role C-type lectin receptor Mincle pneumonic sepsis caused by K. pneumoniae. Methods. Disease progression wild-type and Mincle−/− mice undergoing pulmonary infection was compared. Results. Whereas infected sublethal dose bacteria could resolve clearance regulated...

Neutrophils are the first infiltrating cell type essential for combating pneumoseptic infections by bacterial pathogens including Klebsiella pneumoniae (KPn). Following an infection or injury, removal of apoptotic infiltrates via a highly regulated process called efferocytosis is required restoration homeostasis, but little known regarding effect on this process. Here we demonstrate that KPn impedes efferocytic uptake neutrophils in-vitro and in-vivo in lungs macrophages. This impaired...

Highlights•TRPC1 mediates sterile or infection-induced Ca2+ influx and M1 phenotype in macrophages•ORAI1 the basal macrophages•In patients with SIRS, TRPC1 level correlates inflammatory mediators macrophagesSummaryMacrophage plasticity is essential for innate immunity, but in-depth signaling mechanism(s) regulating their functional phenotypes are ill-defined. Here we report that interferon (IFN) γ priming of naive macrophages induces store-mediated entry inhibition impairs polarization to...

ABSTRACT The available chlamydial genome sequences have made it possible to comprehensively analyze host responses all proteins, which is essential for further understanding of pathogenesis and development effective vaccines. Microplates arrayed with 156 Chlamydia trachomatis fusion proteins were used evaluate antibody in women urogenitally infected C. . Based on both the recognition frequency titer, seven antigens encoded by open reading frames (ORFs) CT089, CT147, CT226, CT681, CT694,...

Sepsis is a complex immune disorder with mortality rate of 20–50% and currently has no therapeutic interventions. It thus critical to identify characterize molecules/factors responsible for its development. We have recently shown that pulmonary infection Francisella results in sepsis As extensive cell death prominent feature sepsis, we hypothesized host endogenous molecules called alarmins released from dead or dying cells cause hyperinflammatory response culminating In the current study...

ABSTRACT Pneumonia is frequently associated with sepsis, characterized by a nonresolving hyperinflammation. However, specific host components of the pulmonary milieu that regulate perpetuation inflammation and tissue destruction observed in this immune disorder are not clearly understood. We examined function Clec4d, an orphan mammalian CLR, Gram negative pneumonic sepsis caused KPn. Whereas WT mice infected sublethal dose bacteria could resolve infection, Clec4d−/− were highly susceptible...

We have previously identified a chlamydia-secreted protein (designated chlamydial proteasome/protease-like activity factor, or CPAF) in the cytosol of chlamydia-infected cells. Although CPAF is known to degrade host transcription factors required for major histocompatibility complex antigen expression cultured cells, it not clear whether produced and maintains similar functions humans infected with organisms. now report that does preexist organisms synthesis requires live organism...

Using antibodies raised with chlamydial fusion proteins, we have localized a protein encoded by hypothetical open reading frame CT813 in the inclusion membrane of Chlamydia trachomatis. The detection C. trachomatis an anti-CT813 antibody was blocked but not unrelated proteins. detected as early 12 h after infection and present during entire growth cycle. All tested serovars from other species expressed protein. Exogenously HeLa cells displayed cytoskeleton-like structure similar to...

Neutrophil extracellular traps (NETs) constitute antimicrobial function of neutrophils but have also been linked to perpetuation inflammation. Despite this evident physiological relevance, mechanistic understanding NET formation is poor. In study, we examined the mechanism by which Mincle, a C-type lectin receptor, regulates formation.NET formation, reactive oxygen species, autophagy activation and intracellular signaling pathways were analyzed in Mincle-sufficient -deficient stimulated...

Macrophages/microglia with M2-activation phenotype are thought to play important anti-inflammatory and tissue reparative functions in the brain, yet molecular bases of their CNS remain be clearly defined. In a preclinical model neurocysticercosis using brain infection parasite <i>Mesocestoides corti</i>, we previously reported presence large numbers M2 cells CNS. this study female mice, report that macrophages parasite-infected display abundant galectin-3 expression. Disease severity was...

The bacterial or host determinants of lethality associated with respiratory Francisella infections are currently unknown. No exo- endotoxins that contribute to the severity this disease have been identified. However, a deregulated immune response upon infection is characterized by an initial 36- 48-h delay followed rapid and excessive inflammatory prior death at 72-120 h. Here, we extend these findings comparing responses between sublethal lethal mice attenuated transposon mutant (Mut) F....

Neurocysticercosis (NCC) is a disease of the central nervous system (CNS) caused by cestode Taenia solium. The infection exhibits long asymptomatic phase, typically lasting 3 to 5 years, before onset symptomatic phase. severity symptoms thought be associated with intensity inflammatory response elicited degenerating parasite. In contrast, phase shows an absence brain inflammation, which presumably due immunosuppressive effects live parasites. However, host factors and/or pathways involved in...

ABSTRACT Neutrophil extracellular trap (NET) formation constitutes an important antimicrobial function of neutrophils that plays a protective role in bacterial pneumonia. Formation reactive oxygen species (ROS) such as highly diffusible hydrogen peroxide (H2O2) is hallmark oxidative stress during inflammatory lung conditions including However, the impact exogenous ROS on NET and signaling pathway involved process not completely understood. Here we demonstrate ROS‐sensing, non‐selective,...

Neutrophil extracellular traps (NETs) function to control infectious agents as well propagate inflammatory response in a variety of disease conditions. DNA damage associated with chromatin decondensation and NACHT domain-leucine-rich repeat-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation have emerged crucial events NET formation, but the link between two processes is unknown. In this study, we demonstrate that poly(ADP-ribose) polymerase-1 (PARP-1), key repair enzyme,...

Sepsis is a complex immune disorder that characterized by systemic hyperinflammation. Alarmins, which are multifunctional endogenous factors, have been implicated in exacerbation of inflammation many disorders including sepsis. Here we show Galectin-9, host β-galactoside binding lectin, functions as an alarmin capable mediating inflammatory response during sepsis resulting from pulmonary infection with Francisella novicida, Gram negative bacterial pathogen. Our results this galectin...

We previously identified a chlamydial protein designated CPAF (chlamydia protease/proteasome-like activity factor) that is secreted into host cell cytosol for degrading transcription factors required major histocompatibility complex antigen expression. Here we report CPAF, synthesized as 70-kDa proprotein, processed two fragments (designated CPAFn and CPAFc) to form intramolecular dimers are much more stable than the naïve CPAF. Precipitation with antibodies recognized removed proteolytic...

Helminth parasites cause persistent infections in humans and yet many infected individuals are asymptomatic. Neurocysticercosis (NCC), a disease of the central nervous system (CNS) caused by cestode Taenia solium, has long asymptomatic phase correlated with an absence brain inflammation. However, mechanisms immune suppression remain poorly understood. Here we report that murine NCC displays lack cell surface maturation markers infiltrating myeloid cells. Furthermore, soluble parasite ligands...

In neurocysticercosis, parasite-induced immune suppressive effects are thought to play an important role in enabling site-specific inhibition of inflammatory responses infections. It is axiomatic that microglia-mediated (M1 proinflammatory) response causes central nervous system inflammation; however, the mechanisms by which helminth parasites modulate microglia activation remain poorly understood. Here, we show display a diminished expression M1-inflammatory mediators such as tumor necrosis...

ABSTRACT We have previously shown that individuals infected with Chlamydia trachomatis can develop a robust antibody response to chlamydia-secreted protein (designated chlamydial proteasome/protease-like activity factor [CPAF]). now report sera collected from these neutralized the proteolytic of CPAF. Depletion serum sample CPAF proteins remove CPAF-specific antibodies effectively blocked neutralization, whereas similar depletion HSP60 failed do so. further demonstrated central region...

The macrophage is a versatile cell type that can sense and respond to particular need based on the conditions of microenvironment. Some studies have recently suggested pathogens directly influence polarization macrophages. As Francisella infections are characterized by intense necrotic infiltrates in lung as well distal sites infection, we sought investigate whether pulmonary could cause alternatively activated macrophages (M2/aaMs). Our results indicate M2/aaM vivo be polarized toward an...

C-type lectin receptors (CLRs), the carbohydrate-recognizing molecules, orchestrate host immune response in homeostasis and inflammation. In present study we examined function of macrophage galactose-type lectin-1 (MGL1), a mammalian CLR, pneumonic sepsis, deadly disorder frequently associated with nonresolving hyperinflammation. murine model sepsis using pulmonary infection Klebsiella pneumoniae, expression MGL1 was upregulated lungs K. pneumoniae-infected mice, deficiency this CLR...