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Journal of Animal Science Jun 2022Biological sex is a major host factor influencing risk for infectious disease-associated mortality, and chronic inflammatory and metabolic diseases. Research in human... (Review)
Review
Biological sex is a major host factor influencing risk for infectious disease-associated mortality, and chronic inflammatory and metabolic diseases. Research in human and rodent models -has revealed sex differences that exist across organ systems during health and disease that may contribute to sex biases in disease risk. Despite the robust and growing literature on the role of sex as a risk factor in human disease, comparatively little attention has been focused on investigating the role of biological sex in disease susceptibility in agriculturally important animal populations such as the pig. To date, comparisons between sexes have focused on carcass composition, growth rate, and feed efficiency in pigs. However, there is a large gap in the literature regarding the effects of biological sex on other integral aspects of health and disease. The objective of this review is to highlight the available literature reporting sex differences in pig health and biology with an emphasis on sex differences in mortality, immunity, and gastrointestinal (GI) physiology and to address biological sex as a significant biological variable in disease risk and research study design. A basic overview of the biology of sex differences including the major hormonal and genetic/chromosomal mechanisms of sexual differentiation and the developmental periods in which sex differences emerge will be covered. This review will also discuss how production-relevant management and environmental factors (e.g., wean age, castration, stress, and nutrition) interact with biological sex to shape host immune and GI development and function. Perceived gaps in knowledge and areas of future research will also be discussed.
Topics: Animals; Disease Susceptibility; Female; Male; Orchiectomy; Research Design; Risk Factors; Sex Characteristics; Sex Factors; Swine; Swine Diseases
PubMed: 35708590
DOI: 10.1093/jas/skac146 -
Neuropsychopharmacology : Official... Jan 2016A swiftly growing volume of literature, comprising both human and animal studies and employing both observational and experimental designs, has documented striking... (Review)
Review
A swiftly growing volume of literature, comprising both human and animal studies and employing both observational and experimental designs, has documented striking individual differences in neurobiological sensitivities to environmental circumstances within subgroups of study samples. This differential susceptibility to social and physical environments operates bidirectionally, in both adverse and beneficial contexts, and results in a minority subpopulation with remarkably poor or unusually positive trajectories of health and development, contingent upon the character of environmental conditions. Differences in contextual susceptibility appear to emerge in early development, as the interactive and adaptive product of genetic and environmental attributes. This paper surveys what is currently known of the mechanisms or mediators of differential susceptibility, at the levels of temperament and behavior, physiological systems, brain circuitry and neuronal function, and genetic and epigenetic variation. It concludes with the assertion that differential susceptibility is inherently grounded within processes of biological moderation, the complexities of which are at present only partially understood.
Topics: Animals; Brain; Disease Susceptibility; Humans; Individuality; Risk Factors; Social Environment; Stress, Psychological; Temperament
PubMed: 26391599
DOI: 10.1038/npp.2015.294 -
Frontiers in Immunology 2018Parasitic helminths are among the most pervasive pathogens of the animal kingdom. To complete their life cycle, these intestinal worms migrate through host tissues... (Review)
Review
Parasitic helminths are among the most pervasive pathogens of the animal kingdom. To complete their life cycle, these intestinal worms migrate through host tissues causing significant damage in their wake. As a result, infection can lead to malnutrition, anemia and increased susceptibility to co-infection. Despite repeated deworming treatment, individuals living in endemic regions remain highly susceptible to re-infection by helminths, but rarely succumb to excessive tissue damage. The chronicity of infection and inability to resist numerous species of parasitic helminths that have co-evolved with their hosts over millenia suggests that mammals have developed mechanisms to tolerate this infectious disease. Distinct from resistance where the goal is to destroy and eliminate the pathogen, disease tolerance is an active process whereby immune and structural cells restrict tissue damage to maintain host fitness without directly affecting pathogen burden. Although disease tolerance is evolutionary conserved and has been well-described in plant systems, only recently has this mode of host defense, in its strictest sense, begun to be explored in mammals. In this review, we will examine the inter- and intracellular networks that support disease tolerance during enteric stages of parasitic helminth infection and why this alternative host defense strategy may have evolved to endure the presence of non-replicating pathogens and maintain the essential functions of the intestine.
Topics: Animals; Asymptomatic Infections; Biological Evolution; Chronic Disease; Disease Resistance; Disease Susceptibility; Gastrointestinal Microbiome; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Intestinal Diseases, Parasitic; Intestines; Parasite Load; Survival Rate
PubMed: 30298071
DOI: 10.3389/fimmu.2018.02128 -
Expert Reviews in Molecular Medicine Jun 2016Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the... (Review)
Review
Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1 show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.
Topics: Age Factors; Animals; Biomarkers; Clinical Trials as Topic; Disease Models, Animal; Disease Progression; Disease Susceptibility; Enterocolitis, Necrotizing; Humans; Immune System; Immunity; Immunologic Factors; Patient Outcome Assessment; Phenotype; Receptors, Immunologic; Receptors, Pattern Recognition; Risk Factors; Severity of Illness Index; Signal Transduction
PubMed: 27341512
DOI: 10.1017/erm.2016.13 -
Translational Research : the Journal of... Jan 2015Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to... (Review)
Review
Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology.
Topics: Animals; DNA Methylation; Disease Susceptibility; Environmental Exposure; Epigenesis, Genetic; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Male; Pregnancy; Translational Research, Biomedical
PubMed: 24657180
DOI: 10.1016/j.trsl.2014.02.003 -
Molecular Therapy : the Journal of the... Jan 2021
Review
Topics: Disease Management; Disease Susceptibility; Humans; Neoplasms
PubMed: 33308440
DOI: 10.1016/j.ymthe.2020.12.005 -
Immunity Jun 2021The interindividual heterogeneity of the immune system likely determines the personal risk for acquiring infections and developing diseases with inflammatory components.... (Review)
Review
The interindividual heterogeneity of the immune system likely determines the personal risk for acquiring infections and developing diseases with inflammatory components. In addition to genetic factors, the immune system's heterogeneity is driven by diverging exposures of leukocytes and their progenitors to infections, vaccinations, and health behavior, including lifestyle-related stimuli such as diet, physical inactivity, and psychosocial stress. We review how such experiences alter immune cell responses to concurrent and subsequent challenges, leading to either improved host resilience or disease susceptibility due to a muted or overzealous immune system, with a primary focus on the contribution of innate immune cells. We explore the involvement of diverse mechanisms, including trained immunity, and their relevance for infections and cardiovascular disease, as these prevalent conditions are heavily influenced by immune cell abundance and phenotypic adaptions. Understanding the mechanistic bases of immune modulations by prior or co-exposures may lead to new therapies targeting dysfunctional inflammation.
Topics: Animals; Cardiovascular Diseases; Disease Susceptibility; Humans; Immune System; Immunity, Innate; Infections; Inflammation; Life Style
PubMed: 34107270
DOI: 10.1016/j.immuni.2021.05.011 -
Nature Reviews. Nephrology Apr 2018Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation,... (Review)
Review
Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis - features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD.
Topics: Animals; Antioxidants; Disease Susceptibility; Longevity; NF-E2-Related Factor 2; Oxidative Stress; Renal Insufficiency, Chronic
PubMed: 29332935
DOI: 10.1038/nrneph.2017.169 -
Annual Review of Immunology Apr 2018Given the many cell types and molecular components of the human immune system, along with vast variations across individuals, how should we go about developing causal... (Review)
Review
Given the many cell types and molecular components of the human immune system, along with vast variations across individuals, how should we go about developing causal and predictive explanations of immunity? A central strategy in human studies is to leverage natural variation to find relationships among variables, including DNA variants, epigenetic states, immune phenotypes, clinical descriptors, and others. Here, we focus on how natural variation is used to find patterns, infer principles, and develop predictive models for two areas: (a) immune cell activation-how single-cell profiling boosts our ability to discover immune cell types and states-and (b) antigen presentation and recognition-how models can be generated to predict presentation of antigens on MHC molecules and their detection by T cell receptors. These are two examples of a shift in how we find the drivers and targets of immunity, especially in the human system in the context of health and disease.
Topics: Animals; Antigen Presentation; Biomarkers; Disease Susceptibility; Epitopes; Genomics; Host-Pathogen Interactions; Humans; Immune System; Immunity; Ligands; Major Histocompatibility Complex; Peptides; Protein Transport; Proteolysis; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes
PubMed: 29677477
DOI: 10.1146/annurev-immunol-042617-053035 -
Open Biology Mar 2019Cellular parabiosis is tissue-based phenotypic suppression of cellular dysfunction by intercellular molecular traffic keeping initiated age-related diseases and... (Review)
Review
Cellular parabiosis is tissue-based phenotypic suppression of cellular dysfunction by intercellular molecular traffic keeping initiated age-related diseases and conditions in long latency. Interruption of cellular parabiosis (e.g. by chronic inflammation) promotes the onset of initiated pathologies. The stability of initiated latent cancers and other age-related diseases (ARD) hints to phenotypically silent genome alterations. I propose that latency in the onset of ageing and ARD is largely due to phenotypic suppression of cellular dysfunctions via molecular traffic among neighbouring cells. Intercellular trafficking ranges from the transfer of ions and metabolites (via gap junctions) to entire organelles (via tunnelling nanotubes). Any mechanism of cell-to-cell communication resulting in functional cross-complementation among the cells is called cellular parabiosis. Such 'cellular solidarity' creates tissue homeostasis by buffering defects and averaging cellular functions within the tissues. Chronic inflammation is known to (i) interrupt cellular parabiosis by the activity of extracellular proteases, (ii) activate dormant pathologies and (iii) shorten disease latency, as in tumour promotion and inflammaging. Variation in cellular parabiosis and protein oxidation can account for interspecies correlations between body mass, ARD latency and longevity. Now, prevention of ARD onset by phenotypic suppression, and healing by phenotypic reversion, become conceivable.
Topics: Aging; Animals; Cell Communication; Disease Susceptibility; Homeostasis; Humans; Inflammation; Longevity; Parabiosis; Reactive Oxygen Species
PubMed: 30914007
DOI: 10.1098/rsob.180250