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The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis
Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.
Journal Article
OP5 A two armed, randomised, controlled exploratory study of adding the ambugard cleaning system to normal deep cleaning procedures in a regional ambulance service
BackgroundAmbulance services transport patients with infections and diseases and could pose a cross transmission risk to patients and staff through environmental contamination. The literature suggests that environmental pathogens are present on ambulances, cleaning is inconsistent and patient/staff impact is difficult to quantify. Eco-Mist developed a dry misting decontamination system for ambulance use called AmbuGard which works in <30 minutes and is 99.9999% effective against common pathogens. The research question is ‘What pathogens are present on North East Ambulance Service ambulances and what impact does adding the AmbuGard to the deep cleaning process make?’MethodsA two armed, randomised controlled trial enrolled fourteen ambulances during their regular 24 week deep clean which were 1:1 randomised to deep cleaning (control arm) or deep cleaning plus AmbuGard (intervention arm). Polywipe swabs were taken before and after cleaning from five locations selected for high rates of contact (steering wheel, shelf, side door grab rail, patient seat armrest, rear door handle/grab rail). Microbiology culture methods identified the presence and amount of bacterial organisms present including the selected pathogens: Enterococcus spp.; Enterobacter spp.; Klebsiella spp.; Staphylococcus aureus; Acinetobacter spp.; Pseudomonas spp.; Clostridium difficile; coagulase-negative staphylococci (CoNS)). The researcher taking the swabs and the laboratory were blinded to the trial arm.ResultsPathogens of interest were found on 10 (71%) vehicles. CoNS were found on all vehicles. Pathogens were found on all locations swabbed. Normal deep cleaning was effective at eliminating pathogens and the addition of AmbuGard showed no obvious improvement in effectiveness.ConclusionPathogens associated with healthcare acquired infections were found throughout all ambulances. Normal deep cleaning was effective and adding AmbuGard showed no obvious improvement. This was a small study at a single point in time. Further research is needed into temporal trends, how to reduce pathogens during normal clinical duties and patient/staff impact.
Journal Article
Functional analyses of small secreted cysteine‐rich proteins identified candidate effectors in Verticillium dahliae
Secreted small cysteine‐rich proteins (SCPs) play a critical role in modulating host immunity in plant–pathogen interactions. Bioinformatic analyses showed that the fungal pathogen Verticillium dahliae encodes more than 100 VdSCPs, but their roles in host–pathogen interactions have not been fully characterized. Transient expression of 123 VdSCP‐encoding genes in Nicotiana benthamiana identified three candidate genes involved in host–pathogen interactions. The expression of these three proteins, VdSCP27, VdSCP113, and VdSCP126, in N. benthamiana resulted in cell death accompanied by a reactive oxygen species burst, callose deposition, and induction of defence genes. The three VdSCPs mainly localized to the periphery of the cell. BAK1 and SOBIR1 (associated with receptor‐like protein) were required for the immunity triggered by these three VdSCPs in N. benthamiana. Site‐directed mutagenesis showed that cysteine residues that form disulphide bonds are essential for the functioning of VdSCP126, but not VdSCP27 and VdSCP113. VdSCP27, VdSCP113, and VdSCP126 individually are not essential for V. dahliae infection of N. benthamiana and Gossypium hirsutum, although there was a significant reduction of virulence on N. benthamiana and G. hirsutum when inoculated with the VdSCP27/VdSCP126 double deletion strain. These results illustrate that the SCPs play a critical role in the V. dahliae–plant interaction via an intrinsic virulence function and suppress immunity following infection. Small cysteine‐rich proteins secreted by Verticillium dahliae play critical roles in interactions with hosts via an intrinsic virulence function and can suppress immunity following infection.
Journal Article
Higher plant diversity promotes higher diversity of fungal pathogens, while it decreases pathogen infection per plant
Fungal plant pathogens are common in natural communities where they affect plant physiology, plant survival, and biomass production. Conversely, pathogen transmission and infection may be regulated by plant community characteristics such as plant species diversity and functional composition that favor pathogen diversity through increases in host diversity while simultaneously reducing pathogen infection via increased variability in host density and spatial heterogeneity. Therefore, a comprehensive understanding of multi‐host–multi‐pathogen interactions is of high significance in the context of biodiversity–ecosystem functioning. We investigated the relationship between plant diversity and aboveground obligate parasitic fungal pathogen (“pathogens” hereafter) diversity and infection in grasslands of a long‐term, large‐scale, biodiversity experiment with varying plant species (1–60 species) and plant functional group diversity (1–4 groups). To estimate pathogen infection of the plant communities, we visually assessed pathogen‐group presence (i.e., rusts, powdery mildews, downy mildews, smuts, and leaf‐spot diseases) and overall infection levels (combining incidence and severity of each pathogen group) in 82 experimental plots on all aboveground organs of all plant species per plot during four surveys in 2006. Pathogen diversity, assessed as the cumulative number of pathogen groups on all plant species per plot, increased log‐linearly with plant species diversity. However, pathogen incidence and severity, and hence overall infection, decreased with increasing plant species diversity. In addition, co‐infection of plant individuals by two or more pathogen groups was less likely with increasing plant community diversity. We conclude that plant community diversity promotes pathogen‐community diversity while at the same time reducing pathogen infection levels of plant individuals.
Journal Article
P794 Signs and symptoms associated with single-pathogen nongonococcal urethritis in men
BackgroundSyndromic management remains the standard nongonococcal urethritis (NGU) treatment approach. Whether pathogen-specific signs/symptoms inform treatment decisions remains unclear. We identified men with single- and mixed-pathogen NGU and assessed for the presence of pathogen-specific signs or symptoms to improve syndromic management.MethodsAs part of an ongoing cohort study (the Idiopathic Urethritis Men’s Project [IUMP]), we recruited men with NGU. NGU was diagnosed by signs and/or symptoms of urethritis, and a urethral Gram stain with ≥5 neutrophils per high-power field without evidence of gram negative intracellular diplococci. Participants underwent a clinical history and physical exam, which documented specific self-reported symptoms and clinician observed signs. Single- and mixed-infections were identified by NAAT testing of first-catch urine for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV), and Ureaplasma urealyticum (UU); five-pathogen-negative cases were classified as idiopathic urethritis (IU).ResultsOne hundred fifty-five men with NGU are included in this analysis. The median age was 28 (range 18–63), 101 (65%) were African American, and 135 (87%) self-identified as heterosexual. The most commonly reported symptom was urethral discharge (92%), followed by burning/tingling (37%), and dysuria (28%). Over half of these men reported more than one symptom (58%). Single-pathogen NGU was detected in 99 (64%) men, mixed-pathogen in 14 (9%), and IU in 42 (27%). For single pathogen NGU, 53 (34%) had CT, 26 (17%) had MG, 3 (2%) had TV, and 17 (11%) had UU. We compared single-pathogen NGU, mixed-infection and IU for differences in signs or symptoms and found no pathogen-specific differences.ConclusionIn men with NGU, no pathogen-specific signs and symptoms were identified that could inform treatment decisions. Pathogen-specific point-of-care tests are needed.DisclosureNo significant relationships.
Journal Article
The human microbiota
The Human Microbiota offers a comprehensive review of all human-associated microbial niches in a single volume, focusing on what modern tools in molecular microbiology are revealing about human microbiota, and how specific microbial communities can be associated with either beneficial effects or diseases. An excellent resource for microbiologists, physicians, infectious disease specialists, and others in the field, the book describes the latest research findings and evaluates the most innovative research approaches and technologies. Perspectives from pioneers in human microbial ecology are provided throughout.
eBook
A small cysteine-rich protein from two kingdoms of microbes is recognized as a novel pathogen-associated molecular pattern
Pathogen-associated molecular patterns (PAMPs) are conserved molecules that are crucial for normal life cycle of microorganisms. However, the diversity of microbial PAMPs is little known. During screening of cell-death-inducing factors from the necrotrophic fungus Valsa mali, we identified a novel PAMP VmE02 that is widely spread in oomycetes and fungi.
Agrobacterium tumefaciens-mediated transient expression or infiltration of recombinant protein produced by Escherichia coli was performed to assay elicitor activity of the proteins tested. Virus-induced gene silencing in Nicotiana benthamiana was used to determine the components involved in VmE02-triggered cell death. The role of VmE02 in virulence and conidiation of V. mali were characterized by gene deletion and complementation.
We found that VmE02, together with some of its homologues from both oomycete and fungal species, exhibited cell-death-inducing activity in N. benthamiana. VmE02-triggered cell death was shown to be dependent on BRI1-ASSOCIATED KINASE-1, SUPPRESSOR OF BIR1- 1, HSP90 and SGT1 in N. benthamiana. Deletion of VmE02 in V. mali greatly attenuated pathogen conidiation but not virulence, and treatment of N. benthamiana with VmE02 enhances plant resistance to Sclerotinia sclerotiorum and Phytophthora capsici.
We conclude that VmE02 is a novel cross-kingdom PAMP produced by several fungi and oomycetes.
Journal Article
Inferring pathogen dynamics from temporal count data: the emergence of Xylella fastidiosa in France is probably not recent
Unravelling the ecological structure of emerging plant pathogens persisting in multi-host systems is challenging. In such systems, observations are often heterogeneous with respect to time, space and host species, and may lead to biases of perception. The biased perception of pathogen ecology may be exacerbated by hidden fractions of the whole host population, which may act as infection reservoirs. We designed a mechanistic-statistical approach to help understand the ecology of emerging pathogens by filtering out some biases of perception. This approach, based on SIR (Susceptible-Infected-Removed) models and a Bayesian framework, disentangles epidemiological and observational processes underlying temporal counting data. We applied our approach to French surveillance data on Xylella fastidiosa, a multi-host pathogenic bacterium recently discovered in Corsica, France. A model selection led to two diverging scenarios: one scenario without a hidden compartment and an introduction around 2001, and the other with a hidden compartment and an introduction around 1985. Thus, Xylella fastidiosa was probably introduced into Corsica much earlier than its discovery, and its control could be arduous under the hidden compartment scenario. From a methodological perspective, our approach provides insights into the dynamics of emerging plant pathogens and, in particular, the potential existence of infection reservoirs.
Journal Article