Histopathology of fish parasite infections – importance for populations

There is a bewildering array of fish parasites and probably all fish species harbour one or more species. Under normal conditions hosts often show little or no signs of infection, either clinically or at the organ and tissue level. All tissues can be infected, including the blood. Coelozoic species generally do not elicit significant host responses. Any developmental stages, however, where these migrate through the host tissues may produce a cellular response if resident for sufficient time. Histozoic parasites are generally more likely to evoke a pathological response since they are invariably in more intimate contact with immunocompetent host cells such as lymphocytes and phagocytes. In some cases, particularly with protistan infections, host response can be dramatic and cause significant disease due to organ dysfunction, with subsequent mortalities. Infections of the external epithelia caused by a variety of parasites including Monogenea and Copepoda are also significant, especially when large numbers are present. Resulting tissue necrosis compromises osmoregulation and facilitates entry of prokaryote infections. Parasites have numerous strategies to evade detection within the host, but even ‘protected’ intracellular forms, e.g. microsporeans and muscle‐invading myxozoans are recognized when they outgrow their accommodation or large cysts rupture, presenting parasite antigens to the host. In most instances, an evolutionary balance has been achieved between the host and the parasite and even when histopathology is evident, this is frequently localized and does not unduly impair performance of the affected organ. Examples include chronic inflammation, granuloma formation and focal fibrosis. This paper outlines the principle histopathological responses to a variety of parasite groups and provides a more detailed treatment of selected parasitic infections in marine and freshwater fish species to illustrate the relative importance of acute and chronic parasitic infections for host survival.     

The Iron age of host–microbe interactions

Microbes exert a major impact on human health and disease by either promoting or disrupting homeostasis, in the latter instance leading to the development of infectious diseases. Such disparate outcomes are driven by the ever-evolving genetic diversity of microbes and the countervailing host responses that minimize their pathogenic impact. Host defense strategies that limit microbial pathogenicity include resistance mechanisms that exert a negative impact on microbes, and disease tolerance mechanisms that sustain host homeostasis without interfering directly with microbes. While genetically distinct, these host defense strategies are functionally integrated, via mechanisms that remain incompletely defined. Here, we explore the general principles via which host adaptive responses regulating iron (Fe) metabolism impact on resistance and disease tolerance to infection.     

感染组学 (infectomics) ———对感染性疾病的总体性和综合性研究

在感染性疾病的范畴内,目前急需一个能有效地、精确地和综合性地研究微生物感染的结构性和功能性基因组学和蛋白质组学 ( 感染组学 ) 的全面方法. 新的方法 ( 如 DNA 和蛋白质微阵列 ) 和传统方法 ( 如分子克隆、 PCR 、基因敲除,加进 (knockin) 和反义术等 ) 的结合将有助于克服今天的困难. 在感染时,微生物及其宿主的全部表型改变 ( 感染组 ) 均由微生物病原体及其宿主的基因组所编码,并在特异的微生物 - 宿主相互作用时的某些环境条件下表达. 微生物及其宿主的全部药物反应 ( 药理组 ) 可用基因组或蛋白质组的方法检出. 分析基因型和表型或表达形式的全基因组方法将最终导致对微生物的发病机理、感染性疾病的快速诊断和控制感染的新策略的全面研究. 感染性疾病中最基本的问题是,如何全面地和综合性地应用感染组学,来了解微生物病原体及其宿主的相互作用.     

Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function

Chronic inflammation in older individuals is thought to contribute to inflammatory, age‐related diseases. Human monocytes are comprised of three subsets (classical, intermediate and nonclassical subsets), and despite being critical regulators of inflammation, the effect of age on the functionality of monocyte subsets remains to be fully defined. In a cross‐sectional study involving 91 healthy male (aged 20–84 years, median 52.4) and 55 female (aged 20–82 years, median 48.3) individuals, we found age was associated with an increased proportion of intermediate and nonclassical monocytes (P = 0.002 and 0.04, respectively) and altered phenotype of specific monocyte subsets (e.g. increased expression of CD11b and decreased expression of CD38, CD62L and CD115). Plasma levels of the innate immune activation markers CXCL10, neopterin (P < 0.001 for both) and sCD163 (P = 0.003) were significantly increased with age. Whilst similar age‐related changes were observed in both sexes, monocytes from women were phenotypically different to men [e.g. lower proportion of nonclassical monocytes (P = 0.002) and higher CD115 and CD62L but lower CD38 expression] and women exhibited higher levels of CXCL10 (P = 0.012) and sCD163 (P < 0.001) but lower sCD14 levels (P < 0.001). Monocytes from older individuals exhibit impaired phagocytosis (P < 0.05) but contain shortened telomeres (P < 0.001) and significantly higher intracellular levels of TNF both at baseline and following TLR4 stimulation (P < 0.05 for both), suggesting a dysregulation of monocyte function in the aged. These data show that aging is associated with chronic innate immune activation and significant changes in monocyte function, which may have implications for the development of age‐related diseases.     

Review: a meta-analysis of GWAS and age-associated diseases

Genome‐Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SNPs associated with many important human diseases, including diseases associated with aging. In an effort to understand the genetics of broad resistance to age‐associated diseases (i.e., ‘wellness’), we performed a meta‐analysis of human GWAS. Toward that end, we compiled 372 GWAS that identified 1775 susceptibility SNPs to 105 unique diseases and used these SNPs to create a genomic landscape of disease susceptibility. This map was constructed by partitioning the genome into 200 kb ‘bins’ and mapping the 1775 susceptibility SNPs to bins based on their genomic location. Investigation of these data revealed significant heterogeneity of disease association within the genome, with 92% of bins devoid of disease‐associated SNPs. In contrast, 10 bins (0.06%) were significantly (P < 0.05) enriched for susceptibility to multiple diseases, 5 of which formed two highly significant peaks of disease association (P < 0.0001). These peaks mapped to the Major Histocompatibility (MHC) locus on 6p21 and the INK4/ARF (CDKN2a/b) tumor suppressor locus on 9p21.3. Provocatively, all 10 significantly enriched bins contained genes linked to either inflammation or cellular senescence pathways, and SNPs near regulators of senescence were particularly associated with disease of aging (e.g., cancer, atherosclerosis, type 2 diabetes, glaucoma). This analysis suggests that germline genetic heterogeneity in the regulation of immunity and cellular senescence influences the human healthspan.     

Noncoding RNAs and chronic inflammation: Micro‐managing the fire within

Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age‐associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. Copyright Line: © 2015 The Authors BioEssays Published by Wiley‐VCH Verlag GmbH & Co. KGaA.     

NONADAPTIVE PROCESSES CAN CREATE THE APPEARANCE OF FACULTATIVE CHEATING IN MICROBES

Adaptations to social life may take the form of facultative cheating, in which organisms cooperate with genetically similar individuals but exploit others. Consistent with this possibility, many strains of social microbes like Myxococcus bacteria and Dictyostelium amoebae have equal fitness in single‐genotype social groups but outcompete other strains in mixed‐genotype groups. Here we show that these observations are also consistent with an alternative, nonadaptive scenario: kin selection‐mutation balance under local competition. Using simple mathematical models, we show that deleterious mutations that reduce competitiveness within social groups (growth rate, e.g.) without affecting group productivity can create fitness effects that are only expressed in the presence of other strains. In Myxococcus, mutations that delay sporulation may strongly reduce developmental competitiveness. Deleterious mutations are expected to accumulate when high levels of kin selection relatedness relax selection within groups. Interestingly, local resource competition can create nonzero “cost” and “benefit” terms in Hamilton's rule even in the absence of any cooperative trait. Our results show how deleterious mutations can play a significant role even in organisms with large populations and highlight the need to test evolutionary causes of social competition among microbes.     

Amplification of autoimmune disease by infection

Reports of infection with certain chronic persistent microbes (herpesviruses or Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that these microbes are reactivated in the setting of immunodeficiency and often target the site of autoimmune inflammation. New experimental animal models demonstrate the principle. A herpesvirus or Chlamydia species can be used to infect mice with induced transient autoimmune diseases. This results in increased disease severity and even relapse. The evidence suggests that the organisms are specifically imported to the inflammatory sites and cause further tissue destruction, especially when the host is immunosuppressed. We review the evidence for the amplification of autoimmune inflammatory disease by microbial infection, which may be a general mechanism applicable to many human diseases. We suggest that patients with autoimmune disorders receiving immunosuppressing drugs should benefit from preventive antiviral therapy.     

CIRCADIAN VARIATION IN ONSET OF ACUTE CARDIOGENIC PULMONARY EDEMA IS INDEPENDENT OF PATIENTS' FEATURES AND UNDERLYING PATHOPHYSIOLOGICAL CAUSES

Background. The present study aimed to confirm the existence of a circadian pattern in the onset of acute pulmonary edema (APE) and to verify whether sex, age, preexisting diseases, and clinical causes determining the event may influence it. Subjects and Methods. The study considered all consecutive cases of APE observed at the St. Anna General Hospital of Ferrara, Italy, during a 7-year period from January 1, 1992, to December 31, 1998. The sample population was divided into subgroups by sex, age (<75 and ≥75 years), presence or absence of diabetes and hypertension, clinical causes determining the event (i.e., acute myocardial infarction (AMI), pulmonary embolism, arrhythmias). The most important associated or concomitant diseases were also considered (i.e., coronary heart disease and angina, previous myocardial infarction, chronic cardiac failure, dilatative cardiopathy, chronic atrial fibrillation, valvular disease, chronic obstructive pulmonary disease, chronic cor pulmonale, malignancy, chronic renal failure). Time of symptom onset of each event was recorded accurately, then tabulated into 24 increments of 1h (e.g., 06:00 to 06:59 was reported as 6 A.M.). For statistical chronobiological analysis, partial Fourier series were used. Results. During the 7-year period, 1321 consecutive cases of APE in 1014 different subjects were observed. The majority of events occurred at night, and statistical analysis showed a 24h rhythmicity both in the total sample population and in all considered subgroups, with the only exception being patients with pulmonary embolism and arrhythmias, for which the small number of cases made the study of rhythms in APE impossible. Conclusions. The nighttime preference in the occurrence of APE appears to be quite independent of all demographic features or underlying pathophysiological causes. (Chronobiology International, 17(5), 705–715, 2000)     

Bacterial inhibition of inflammatory responses via TLR‐independent mechanisms

Identification of cellular processes modulated by microbial organisms that undermine and disarm mammalian host defences against bacterial invaders has been the focus of significant biomedical research. In this microreview we will illustrate the role of bacterial N‐acyl homoserine lactones (AHL) as a strategy utilized by Gram‐negative bacterial pathogens to enable colonization of the host through AHL‐mediated inhibition of inflammation induced via innate immune receptor mechanisms. We will also highlight some of the signalling pathways in which the study of AHL‐mediated effects on mammalian cells might lead to the discovery of global underlying principles linking inflammation and immunity to many chronic human diseases, including cancer and obesity.     

Mitigating amphibian chytridiomycosis with bioaugmentation: characteristics of effective probiotics and strategies for their selection and use

Probiotic therapy through bioaugmentation is a feasible disease mitigation strategy based on growing evidence that microbes contribute to host defences of plants and animals. Amphibians are currently threatened by the rapid global spread of the pathogen, Batrachochytrium dendrobatidis (Bd), which causes the disease chytridiomycosis. Bioaugmentation of locally occurring protective bacteria on amphibians has mitigated this disease effectively in laboratory trials and one recent field trial. Areas still naïve to Bd provide an opportunity for conservationists to proactively implement probiotic strategies to prevent further amphibian declines. In areas where Bd is endemic, bioaugmentation can facilitate repatriation of susceptible amphibians currently maintained in assurance colonies. Here, we synthesise the current research in amphibian microbial ecology and bioaugmentation to identify characteristics of effective probiotics in relation to their interactions with Bd, their host, other resident microbes and the environment. To target at‐risk species and amphibian communities, we develop sampling strategies and filtering protocols that result in probiotics that inhibit Bd under ecologically relevant conditions and persist on susceptible amphibians. This filtering tool can be used proactively to guide amphibian disease mitigation and can be extended to other taxa threatened by emerging infectious diseases.     

Global distribution of outbreaks of water-associated infectious diseases

Background

Water plays an important role in the transmission of many infectious diseases, which pose a great burden on global public health. However, the global distribution of these water-associated infectious diseases and underlying factors remain largely unexplored.

Methods and Findings

Based on the Global Infectious Disease and Epidemiology Network (GIDEON), a global database including water-associated pathogens and diseases was developed. In this study, reported outbreak events associated with corresponding water-associated infectious diseases from 1991 to 2008 were extracted from the database. The location of each reported outbreak event was identified and geocoded into a GIS database. Also collected in the GIS database included geo-referenced socio-environmental information including population density (2000), annual accumulated temperature, surface water area, and average annual precipitation. Poisson models with Bayesian inference were developed to explore the association between these socio-environmental factors and distribution of the reported outbreak events. Based on model predictions a global relative risk map was generated. A total of 1,428 reported outbreak events were retrieved from the database. The analysis suggested that outbreaks of water-associated diseases are significantly correlated with socio-environmental factors. Population density is a significant risk factor for all categories of reported outbreaks of water-associated diseases; water-related diseases (e.g., vector-borne diseases) are associated with accumulated temperature; water-washed diseases (e.g., conjunctivitis) are inversely related to surface water area; both water-borne and water-related diseases are inversely related to average annual rainfall. Based on the model predictions, “hotspots” of risks for all categories of water-associated diseases were explored.

Conclusions

At the global scale, water-associated infectious diseases are significantly correlated with socio-environmental factors, impacting all regions which are affected disproportionately by different categories of water-associated infectious diseases.     

Bestimmung der Verdaulichkeit der Rohnährstoffe,Basischen und Schwefelhaltigen Aminosäuren von Natürlich und Technisch Getrockneten Rotkleeblättern an Kolostomierten Legehennen

Domesticated animals all over the world are subjected to a wide variety of environmental conditions and challenges. Any deviation from “normal”; may result in adaptive behavior of which changes in feed intake or feed intake pattern is by far the most important. Adaptive behavior may further include influences on passage rate of feed residues through the digestive tract, resulting in changes in digestibility. Adaptive behavior may also result in changes in heat production, either to maintain body temperature constant, or as a result of an elevated body temperature.

Important environmental challenges are infectious diseases. Mild (sub‐clinical) infections usually result in reduced performance, without affecting feed intake or digestibility. Severe infections may disrupt the barriers between the internal metabolism and the respiratory and/or digestive tract, resulting in severe losses of energy and protein. This situation is notably apparent in severe infections with parasites of the gastrointestinal tract and may be associated with severe protein losses. Feeding high protein diets may partly alleviate the negative effects.

Contamination of air, water and feed may occasionally cause problems in farm animals. Such contamination may include pathogenic microbes, toxic secondary fungal metabolites and heavy metals. Negative effects associated with such contamination often show an impaired reproductive efficiency, but their influence on the utilization of energy and nutrients is not well documented.     

Infectomics: genomics and proteomics of microbial infections

The completion of genomic sequences is the greatest triumph of molecular reductionism since the discovery of the DNA double helix in 1953. However, the utility of reductionism is becoming limited and holistic approaches, including theories and techniques, are desperately needed in the postgenomic era. In the field of infectious diseases there is an urgent need for global approaches that can efficiently, precisely and integratively study structural and functional genomics and proteomics of microbial infections (infectomics). The combination of new (e.g. DNA and protein microarrays) and traditional approaches (e.g. cloning, PCR, gene knockout and knockin, and antisense) will help overcome the challenges we are facing today. We assume that the global phenotypic changes (infectomes) in microbes and their host during infections are encoded by the genomes of microbial pathogens and their hosts, expressed in certain environmental conditions devoted to specific microbe-host interactions. Global drug responses (pharmacomes) in microbes and their host can be detected by genomic and proteomic approaches. Genome-wide approaches to genotyping and phenotyping or expression profiling will eventually lead to global dissection of microbial pathogenesis, efficient and rapid diagnosis of infectious diseases, and the development of novel strategies to control infections. The key fundamental issue of infectious diseases is how to globally and integratively understand the interactions between microbial pathogens and their hosts by using infectomics. In this review, we focus on the events that are considered important in infectomics. Electronic Publication     

Specialisation and extinction: Cope's law revisited

Some lineages, specific and supraspecific, tend to be extinction‐prone, others extinction‐resistant in the face of environmental change. Recent attention to the theoretical causes of extinction has focused almost entirely on physical (exogenous) factors. In most higher taxa, species appearing first are commonly characterised by having small to average size, and relatively generalised morphology. Species appearing later in many groups frequently include forms characterised by significant morphologic departures from the early‐appearing, but persistent norm. Such specialised features may include excessive ornamentation such as spinosity, and large, even giant size. Generalists within a genus occupy a considerable spectrum of environments (and communities), but specialists in the same genus tend to occur in a single environment and a single community. Particularly in the benthos, specialists tend to be biogeographically endemic and generalists cosmopolitan, unless the spectrum of environments is extensive and there are no barriers to reproductive communication. Not all forms becoming extinct show morphologic, ecologic or biogeographic evidence of specialisation; this is not surprising since specialisations are not restricted to the skeletal system alone, nor to ecologic and biogeographic characteristics. Specialised community types (e.g. the reef complex of communities, varied pelmatozoan and bryozoan thickets, and sponge forests) are far more extinction‐prone than their more generalised level bottom antecedents. Such biological specialisations ‐ connected with endogenous factors and characteristics of some species ‐ may sometimes be recognised in the palaeontologic record.     

Anti‐inflammatory effects of eriocitrin against the dextran sulfate sodium–induced experimental colitis in murine model

Inflammatory bowel disease (IBD) is a continual ailment condition which engrosses the entire alimentary canal. The IBD can be primarily distinguished into two forms, ulcerative colitis, and Crohn's disease. The major symptoms of IBD include pustules or abscesses, severe abdominal pain, diarrhea, fistula, and stenosis, which may directly affect the patient's quality of life. A variety of mediators can stimulate the circumstances of IBD, some examples include infections by microbes such as bacteria, perturbation of the immune system and the surrounding environment of the intestines. Severe colitis was stimulated in the experimental animals through administering 4% dextran sulfate sodium (DSS) which is mixed in water ad libitum for 6 days. Eriocitrin (30 mg/kg) was then administered to the experimental animals followed by the induction of severe colitis to evaluate the therapeutic prospective of eriocitrin against the colon inflammation stimulated by DSS. In this study, eriocitrin (30 mg/kg) demonstrated significant (P < .05) attenuation activity against the DSS‐stimulated severe colitis in experimental animals. Eriocitrin counteracted all of the clinical deleterious effects induced by DSS, such as body‐weight loss, colon shortening, histopathological injury, accretion of infiltrated inflammatory cells at the inflamed region and the secretion of inflammatory cytokines. The results clearly showed that eriocitrin effectively attenuated DSS‐induced acute colitis in experimental animals.     

Streptococcal toxins: role in pathogenesis and disease

Group A Streptococcus (Streptococcus pyogenes), group B Streptococcus (Streptococcus agalactiae) and Streptococcus pneumoniae (pneumococcus) are host‐adapted bacterial pathogens among the leading infectious causes of human morbidity and mortality. These microbes and related members of the genus Streptococcus produce an array of toxins that act against human cells or tissues, resulting in impaired immune responses and subversion of host physiological processes to benefit the invading microorganism. This toxin repertoire includes haemolysins, proteases, superantigens and other agents that ultimately enhance colonization and survival within the host and promote dissemination of the pathogen.