scholarly journals The Role of Innate Immune Response and Microbiome in Resilience of Dairy Cattle to Disease: The Mastitis Model

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1397
Author(s):  
Valerio Bronzo ◽  
Vincenzo Lopreiato ◽  
Federica Riva ◽  
Massimo Amadori ◽  
Giulio Curone ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Immune System ◽  
Inflammatory Response ◽  
Milk Yield ◽  
Innate Immune System ◽  
Control Strategies ◽  
Animal Health ◽  
Innate Immune ◽  
Immune Functions ◽  
Microbial Agents

Animal health is affected by many factors such as metabolic stress, the immune system, and epidemiological features that interconnect. The immune system has evolved along with the phylogenetic evolution as a highly refined sensing and response system, poised to react against diverse infectious and non-infectious stressors for better survival and adaptation. It is now known that high genetic merit for milk yield is correlated with a defective control of the inflammatory response, underlying the occurrence of several production diseases. This is evident in the mastitis model where high-yielding dairy cows show high disease prevalence of the mammary gland with reduced effectiveness of the innate immune system and poor control over the inflammatory response to microbial agents. There is growing evidence of epigenetic effects on innate immunity genes underlying the response to common microbial agents. The aforementioned agents, along with other non-infectious stressors, can give rise to abnormal activation of the innate immune system, underlying serious disease conditions, and affecting milk yield. Furthermore, the microbiome also plays a role in shaping immune functions and disease resistance as a whole. Accordingly, proper modulation of the microbiome can be pivotal to successful disease control strategies. These strategies can benefit from a fundamental re-appraisal of native cattle breeds as models of disease resistance based on successful coping of both infectious and non-infectious stressors.

scholarly journals The Autumn Low Milk Yield Syndrome in High Genetic Merit Dairy Cattle: The Possible Role of a Dysregulated Innate Immune Response

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 388
Author(s):  
Massimo Amadori ◽  
Chiara Spelta
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Dairy Cattle ◽  
Memory Effect ◽  
Milk Yield ◽  
Innate Immune System ◽  
Innate Immune ◽  
Effective Control ◽  
Dry Period ◽  
Genetic Merit

The analysis of milk yield data shows that high genetic merit dairy cows do not express their full production potential in autumn. Therefore, we focused on metabolic stress and inflammatory response in the dry and peripartum periods as possible causes thereof. It was our understanding that some cows could not cope with the stress imposed by their physiological and productive status by means of adequate adaptation strategies. Accordingly, this study highlights the noxious factors with a potential to affect cows in the above transition period: hot summer climate, adverse genetic traits, poor coping with unfavorable environmental conditions, outright production diseases and consequences thereof. In particular, the detrimental effects in the dry period of overcrowding, photoperiod change and heat stress on mammary gland development and milk production are highlighted in the context of the autumn low milk yield syndrome. The latter could be largely accounted for by a “memory” effect on the innate immune system induced in summer by diverse stressors after dry-off, according to strong circumstantial and indirect experimental evidence. The “memory” effect is based on distinct epigenetic changes of innate immunity genes, as already shown in cases of bovine mastitis. Following a primary stimulation, the innate immune system would be able to achieve a state known as “trained immunity”, a sort of “education” which modifies the response to the same or similar stressors upon a subsequent exposure. In our scenario, the “education” of the innate immune system would induce a major shift in the metabolism of inflammatory cells following their reprogramming. This would entail a higher basal consumption of glucose, in competition with the need for the synthesis of milk. Also, there is strong evidence that the inflammatory response generated in the dry period leads to a notable reduction of dry matter intake after calving, and to a reduced efficiency of oxidative phosphorylation in mitochondria. On the whole, an effective control of the stressors in the dry period is badly needed for better disease control and optimal production levels in dairy cattle.

Effect of traditional Korean medicinal (TKM) triherbal extract on the innate immune system and disease resistance in Paralichthys olivaceus against Uronema marinum

2010 ◽  
Vol 170 (1-2) ◽  
pp. 1-7 ◽  
Author(s):  
Ramasamy Harikrishnan ◽  
Jaehyun Heo ◽  
Chellam Balasundaram ◽  
Man-Chul Kim ◽  
Ju-Sang Kim ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Immune System ◽  
Innate Immune System ◽  
Paralichthys Olivaceus ◽  
Innate Immune

scholarly journals Inhibition of Toll-like Receptor and Cytokine Signaling—A Unifying Theme in Ischemic Tolerance

2004 ◽  
Vol 24 (11) ◽  
pp. 1288-1304 ◽  
Author(s):  
Katalin Karikó ◽  
Drew Weissman ◽  
Frank A. Welsh
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Lipid Rafts ◽  
Inflammatory Cytokines ◽  
Innate Immune System ◽  
Endotoxin Tolerance ◽  
Ischemic Tolerance ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
The Brain

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines, such as TNF, IL-1β and IL-6, that alter blood flow and increase vascular permeability, thus leading to secondary ischemia and accumulation of immune cells in the brain. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs) that recognize host-derived molecules released from injured tissues and cells. Recently, great strides have been made in understanding the regulation of the innate immune system, particularly the signaling mechanisms of TLRs. Negative feedback inhibitors of TLRs and inflammatory cytokines have now been identified and characterized. It is also evident that lipid rafts exist in membranes and play a role in receptor-mediated inflammatory signaling events. In the present review, using this newly available large body of knowledge, we take a fresh look at studies of ischemic tolerance. Based on this analysis, we recognize a striking similarity between ischemic tolerance and endotoxin tolerance, an immune suppressive state characterized by hyporesponsiveness to lipopolysaccharide (LPS). In view of this analogy, and considering recent discoveries related to molecular mechanisms of endotoxin tolerance, we postulate that inhibition of TLR and proinflammatory cytokine signaling contributes critically to ischemic tolerance in the brain and other organs. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Tolerance can be established with two temporal profiles: (i) a rapid form in which the trigger induces tolerance to ischemia within minutes and (ii) a delayed form in which development of protection takes several hours or days and requires de-novo protein synthesis. The rapid form of tolerance is achieved by direct interference with membrane fluidity, causing disruption of lipid rafts leading to inhibition of TLR/cytokine signaling pathways. In the delayed form of tolerance, the preconditioning stimulus first triggers the TLR/cytokine inflammatory pathways, leading not only to inflammation but also to simultaneous upregulation of feedback inhibitors of inflammation. These inhibitors, which include signaling inhibitors, decoy receptors, and anti-inflammatory cytokines, reduce the inflammatory response to a subsequent episode of ischemia. This novel interpretation of the molecular mechanism of ischemic tolerance highlights new avenues for future investigation into the prevention and treatment of stroke and related diseases.

scholarly journals A novel GH secretagogue, A233, exhibits enhanced growth activity and innate immune system stimulation in teleosts fish

2012 ◽  
Vol 214 (3) ◽  
pp. 409-419 ◽  
Author(s):  
Rebeca Martinez ◽  
Kenia Ubieta ◽  
Fidel Herrera ◽  
Alina Forellat ◽  
Reynold Morales ◽  
...  
Keyword(s):  
Immune System ◽  
Molecular Modeling ◽  
Innate Immune System ◽  
Fish Larvae ◽  
Physiological State ◽  
Head Kidney ◽  
Innate Immune ◽  
Superoxide Production ◽  
Immune Functions

In teleosts fish, secretion of GH is regulated by several hypothalamic factors that are influenced by the physiological state of the animal. There is an interaction between immune and endocrine systems through hormones and cytokines. GH in fish is involved in many physiological processes that are not overtly growth related, such as saltwater osmoregulation, antifreeze synthesis, and the regulation of sexual maturation and immune functions. This study was conducted to characterize a decapeptide compound A233 (GKFDLSPEHQ) designed by molecular modeling to evaluate its function as a GH secretagogue (GHS). In pituitary cell culture, the peptide A233 induces GH secretion and it is also able to increase superoxide production in tilapia head–kidney leukocyte cultures. This effect is blocked by preincubation with the GHS receptor antagonist [d-Lys3]-GHRP6. Immunoneutralization of GH by addition of anti-tilapia GH monoclonal antibody blocked the stimulatory effect of A233 on superoxide production. These experiments propose a GH-mediated mechanism for the action of A233. The in vivo biological action of the decapeptide was also demonstrated for growth stimulation in goldfish and tilapia larvae (P<0.001). Superoxide dismutase levels, antiprotease activity, and lectin titer were enhanced in tilapia larvae treated with this novel molecule. The decapeptide A233 designed by molecular modeling is able to function as a GHS in teleosts and enhance parameters of the innate immune system in the fish larvae.

scholarly journals Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

2017 ◽  
Vol 114 (13) ◽  
pp. E2758-E2765 ◽  
Author(s):  
Alexey V. Kostarnoy ◽  
Petya G. Gancheva ◽  
Bernd Lepenies ◽  
Amir I. Tukhvatulin ◽  
Alina S. Dzharullaeva ◽  
...  
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Innate Immune ◽  
Sterile Inflammation ◽  
Skin Damage ◽  
Cholesterol Sulfate ◽  
Local Inflammatory Response

Sterile (noninfected) inflammation underlies the pathogenesis of many widespread diseases, such as allergies and autoimmune diseases. The evolutionarily conserved innate immune system is considered to play a key role in tissue injury recognition and the subsequent development of sterile inflammation; however, the underlying molecular mechanisms are not yet completely understood. Here, we show that cholesterol sulfate, a molecule present in relatively high concentrations in the epithelial layer of barrier tissues, is selectively recognized by Mincle (Clec4e), a C-type lectin receptor of the innate immune system that is strongly up-regulated in response to skin damage. Mincle activation by cholesterol sulfate causes the secretion of a range of proinflammatory mediators, and s.c. injection of cholesterol sulfate results in a Mincle-mediated induction of a severe local inflammatory response. In addition, our study reveals a role of Mincle as a driving component in the pathogenesis of allergic skin inflammation. In a well-established model of allergic contact dermatitis, the absence of Mincle leads to a significant suppression of the magnitude of the skin inflammatory response as assessed by changes in ear thickness, myeloid cell infiltration, and cytokine and chemokine secretion. Taken together, our results provide a deeper understanding of the fundamental mechanisms underlying sterile inflammation.

scholarly journals Genetic variability associated with OAS1 expression in myeloid cells increases the risk of Alzheimer's disease and severe COVID-19 outcomes

2021 ◽  
Author(s):  
Naciye Magusali ◽  
Andrew C Graham ◽  
Thomas M Piers ◽  
Pantila Panichnantakul ◽  
Umran Yaman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Critical Illness ◽  
Inflammatory Response ◽  
Innate Immune System ◽  
Transcriptional Network ◽  
Innate Immune ◽  
Genome Wide Association Studies ◽  
Oligoadenylate Synthetase

Genome-wide association studies of late-onset Alzheimer's disease (AD) have highlighted the importance of variants associated with genes expressed by the innate immune system in determining risk for AD. Recently, we and others have shown that genes associated with variants that confer risk for AD are significantly enriched in transcriptional networks expressed by amyloid-responsive microglia. This allowed us to predict new risk genes for AD, including the interferon-responsive oligoadenylate synthetase 1 (OAS1). However, the function of OAS1 within microglia and its genetic pathway are not known. Using genotyping from 1,313 individuals with sporadic AD and 1,234 control individuals, we confirm that the OAS1 variant, rs1131454, is associated with increased risk for AD and decreased OAS1 expression. Moreover, we note that the same locus was recently associated with critical illness in response to COVID-19, linking variants that are associated with AD and a severe response to COVID-19. By analysing single-cell RNA-sequencing (scRNA-seq) data of isolated microglia from APPNL-G-F knock-in and wild-type C57BL/6J mice, we identify a transcriptional network that is significantly upregulated with age and amyloid deposition, and contains the mouse orthologue Oas1a, providing evidence that Oas1a plays an age-dependent function in the innate immune system. We identify a similar interferon-related transcriptional network containing OAS1 by analysing scRNA-seq data from human microglia isolated from individuals with AD. Finally, using human iPSC-derived microglial cells (h-iPSC-Mg), we see that OAS1 is required to limit the pro-inflammatory response of microglia. When stimulated with interferon-gamma (IFN-γ), we note that cells with lower OAS1 expression show an exaggerated pro-inflammatory response, with increased expression and secretion of TNF-α. Collectively, our data support a link between genetic risk for AD and susceptibility to critical illness with COVID-19 centred on OAS1 and interferon signalling, a finding with potential implications for future treatments of both AD and COVID-19, and the development of biomarkers to track disease progression.

scholarly journals Effects of mannose-binding lectin on pulmonary gene expression and innate immune inflammatory response to ozone

2016 ◽  
Vol 311 (2) ◽  
pp. L280-L291 ◽  
Author(s):  
Jonathan M. Ciencewicki ◽  
Kirsten C. Verhein ◽  
Kevin Gerrish ◽  
Zachary R. McCaw ◽  
Jianying Li ◽  
...  
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Innate Immune System ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Innate Immune ◽  
Gene Sets ◽  
Mannose Binding ◽  
Gene Transcripts ◽  
Binding Lectin

Ozone is a common, potent oxidant pollutant in industrialized nations. Ozone exposure causes airway hyperreactivity, lung hyperpermeability, inflammation, and cell damage in humans and laboratory animals, and exposure to ozone has been associated with exacerbation of asthma, altered lung function, and mortality. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose-binding lectin (MBL), an innate immunity serum protein, contributes to the proinflammatory events caused by ozone-mediated activation of the innate immune system. Wild-type ( Mbl+/+) and MBL-deficient ( Mbl−/−) mice were exposed to ozone (0.3 ppm) for up to 72 h, and bronchoalveolar lavage fluid was examined for inflammatory markers. Mean numbers of eosinophils and neutrophils and levels of the neutrophil attractants C-X-C motif chemokines 2 [ Cxcl2 (major intrinsic protein 2)] and 5 [ Cxcl5 (limb expression, LIX)] in the bronchoalveolar lavage fluid were significantly lower in Mbl−/− than Mbl+/+ mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in transcript response profiles and networks at baseline [e.g., nuclear factor erythroid-related factor 2 (NRF2)-mediated oxidative stress response] and after exposure (e.g., humoral immune response) between Mbl+/+ and Mbl−/− mice. The microarray data were further analyzed to discover several informative differential response patterns and subsequent gene sets, including the antimicrobial response and the inflammatory response. We also used the lists of gene transcripts to search the LINCS L1000CDS2 data sets to identify agents that are predicted to perturb ozone-induced changes in gene transcripts and inflammation. These novel findings demonstrate that targeted deletion of Mbl caused differential levels of inflammation-related gene sets at baseline and after exposure to ozone and significantly reduced pulmonary inflammation, thus indicating an important innate immunomodulatory role of the gene in this model.

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