A Glutathione Peroxidase Gene from Litopenaeus vannamei Is Involved in Oxidative Stress Responses and Pathogen Infection Resistance

In shrimp, several glutathione peroxidase (GPX) genes have been cloned and functionally studied. Increasing evidence suggests the genes’ involvement in white spot syndrome virus (WSSV)- or Vibrio alginolyticus-infection resistance. In the present study, a novel GXP gene (LvGPX3) was cloned in Litopenaeus vannamei. Promoter of LvGPX3 was activated by NF-E2-related factor 2. Further study showed that LvGPX3 expression was evidently accelerated by oxidative stress or WSSV or V. alginolyticus infection. Consistently, downregulated expression of LvGPX3 increased the cumulative mortality of WSSV- or V. alginolyticus-infected shrimp. Similar results occurred in shrimp suffering from oxidative stress. Moreover, LvGPX3 was important for enhancing Antimicrobial peptide (AMP) gene expression in S2 cells with lipopolysaccharide treatment. Further, knockdown of LvGPX3 expression significantly suppressed expression of AMPs, such as Penaeidins 2a, Penaeidins 3a and anti-lipopolysaccharide factor 1 in shrimp. AMPs have been proven to be engaged in shrimp WSSV- or V. alginolyticus-infection resistance; it was inferred that LvGPX3 might enhance shrimp immune response under immune challenges, such as increasing expression of AMPs. The regulation mechanism remains to be further studied.

Leukocyte cytokine responses in adult patients with mitochondrial DNA defects

Patients with oxidative phosphorylation (OxPhos) defects causing mitochondrial diseases appear particularly vulnerable to infections. Although OxPhos defects modulate cytokine production in vitro and in animal models, little is known about how circulating leukocytes of patients with inherited mitochondrial DNA (mtDNA) defects respond to acute immune challenges. In a small cohort of healthy controls (n=21) and patients (n=12) with either the m.3243A>G mutation or single, large-scale mtDNA deletions, we examined: i) cytokine responses (IL-6, TNF-α, IL-1β) in response to acute lipopolysaccharide (LPS) exposure, and ii) sensitivity to the immunosuppressive effects of glucocorticoid signaling (dexamethasone) on cytokine production. In dose-response experiments to determine the half-maximal effective LPS concentration (EC50), relative to controls, leukocytes from patients with mtDNA deletions showed 174 -179% lower responses for IL-6 and IL-1β (pIL-6=0.031, pIL-1β=0.009). Moreover, IL-6 response to LPS in presence of GC was also blunted in cells from patients with mtDNA deletions (pIL-6=0.006), but not in leukocytes from patients with the m.3243A>G mutation. Overall, these ex vivo data provide preliminary evidence that some systemic OxPhos defects may compromise immune cytokine responses and glucocorticoid sensitivity. Further work in larger cohorts is needed to define the nature of immune dysregulation in patients with mitochondrial disease, and their potential implications for disease phenotypes.

Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells

Microbe-associated molecular patterns, such as lipopolysaccharide (LPS) and β-glucan (BG), are surrogates of immune challenges like bacterial and fungal infections, respectively. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), supports the immune system in its fight against infections. This study investigated significant and prominent changes of the transcriptome of human peripheral blood mononuclear cells that immediately after isolation are exposed to 1,25(OH)2D3-modulated immune challenges over a time frame of 24-48 h. In this in vitro study design, most LPS and BG responsive genes are downregulated and their counts are drastically reduced when cells are treated 24 h after, 24 h before or in parallel with 1,25(OH)2D3. Interestingly, only a 1,25(OH)2D3 pre-treatment of the LPS challenge results in a majority of upregulated genes. Based on transcriptome-wide data both immune challenges display characteristic differences in responsive genes and their associated pathways, to which the actions of 1,25(OH)2D3 often oppose. The joined BG/1,25(OH)2D3 response is less sensitive to treatment sequence than that of LPS/1,25(OH)2D3. In conclusion, the functional consequences of immune challenges are significantly modulated by 1,25(OH)2D3 but largely depend on treatment sequence. This may suggest that a sufficient vitamin D status before an infection is more important than vitamin D supplementation afterwards.

Aging Immune System and Its Correlation With Liability to Severe Lung Complications

Aging is considered to be a decline in physical and physiological events that extensively affect the body's immunity, and is linked with deterioration in both innate and adaptive immune responses. The immune system exhibits profound age-associated variations, known as immunosenescence, comprising a significantly low production of B and T lymphocytes in bone marrow and thymus, a decreased function of mature lymphocytes in secondary lymphoid tissues, a decrease in the synthesis of fresh naïve T cells, and reduced activation of T cells. Elderly individuals face a greater risk for many diseases particularly respiratory diseases due to their poor response to immune challenges as vigorously as the young. The current review explored the aging immune system, highlight the mortality rates of severe lung complications, such as pneumonia, COVID-19, asthma, COPD, lung cancer, IPF, and acute lung injury, and their correlation with aging immunity. This study can be helpful in better understanding the pathophysiology of aging, immune responses, and developing new approaches to improve the average age of the elderly population.

Effects of Local and Systemic Immune Challenges on the Expression of Selected Salivary Genes in the Malaria Mosquito Anopheles coluzzii

Salivary glands play a crucial tripartite role in mosquito physiology. First, they secrete factors that greatly facilitate both sugar and blood meal acquisition. Second, the transmission of pathogens (parasites, bacteria and viruses) to the vertebrate host requires both the recognition and invasion of the salivary glands. Third, they produce immune factors that both protect the organ from invading pathogens and are also able to exert their activity in the crop and the midgut when saliva is re-ingested during feeding. Studies on mosquito sialomes have revealed the presence of several female and/or male salivary gland-specific or enriched genes whose function is completely unknown so far. We focused our attention on these orphan genes, and we selected, according to sequence and structural features, a shortlist of 11 candidates with potential antimicrobial properties. Afterwards, using qPCR, we investigated their expression profile at 5 and 24 h after an infectious sugar meal (local challenge) or thoracic microinjection (systemic challenge) of Gram-negative (Escherichia coli, EC) or Gram-positive (Staphylococcus aureus, SA) bacteria. We observed a general increase in the transcript abundance of our salivary candidates between 5 and 24 h after local challenge. Moreover, transcriptional modulation was determined by the nature of the stimulus, with salivary gland-enriched genes (especially hyp15 upon SA stimulus) upregulated shortly after the local challenge and later after the systemic challenge. Overall, this work provides one of the first contributions to the understanding of the immune role of mosquito salivary glands. Further characterization of salivary candidates whose expression is modulated by immune challenge may help in the identification of possible novel antimicrobial peptides.

Oxidative damage increases with degree of simulated bacterial infection, but not ectoparasitism, in tree swallow nestlings

ABSTRACT The purpose of mounting an immune response is to destroy pathogens, but this response comes at a physiological cost, including the generation of oxidative damage. However, many studies on the effects of immune challenges employ a single high dose of a simulated infection, meaning that the consequences of more mild immune challenges are poorly understood. We tested whether the degree of immunological challenge in tree swallows (Tachycineta bicolor) affects oxidative physiology and body mass, and whether these metrics correlate with parasitic nest mite load. We injected 14 day old nestlings with 0, 0.01, 0.1 or 1 mg lipopolysaccharide (LPS) per kg body mass, then collected a blood sample 24 h later to quantify multiple physiological metrics, including oxidative damage (i.e. d-ROMs), circulating amounts of triglyceride and glycerol, and levels of the acute phase protein haptoglobin. After birds had fledged, we identified and counted parasitic nest mites (Dermanyssus spp. and Ornithonyssus spp.). We found that only nestlings injected with 1 mg LPS kg−1 body mass, which is a common dosage in ecoimmunological studies, lost more body mass than individuals from other treatment groups. However, every dose of LPS resulted in a commensurate increase in oxidative damage. Parasitic mite abundance had no effect on oxidative damage across treatments. The amount of oxidative damage correlated with haptoglobin levels, suggesting compensatory mechanisms to limit self-damage during an immune response. We conclude that while only the highest-intensity immune challenges resulted in costs related to body mass, even low-intensity immune challenges result in detectable increases in oxidative damage.

Immune challenges increase network centrality in a queenless ant

Social animals display a wide range of behavioural defences against infectious diseases, some of which increase social contacts with infectious individuals (e.g. mutual grooming), while others decrease them (e.g. social exclusion). These defences often rely on the detection of infectious individuals, but this can be achieved in several ways that are difficult to differentiate. Here, we combine non-pathogenic immune challenges with automated tracking in colonies of the clonal raider ant to ask whether ants can detect the immune status of their social partners and to quantify their behavioural responses to this perceived infection risk. We first show that a key behavioural response elicited by live pathogens (allogrooming) can be qualitatively recapitulated by immune challenges alone. Automated scoring of interactions between all colony members reveals that this behavioural response increases the network centrality of immune-challenged individuals through a general increase in physical contacts. These results show that ants can detect the immune status of their nest-mates and respond with a general ‘caring’ strategy, rather than avoidance, towards social partners that are perceived to be infectious. Finally, we find no evidence that changes in cuticular hydrocarbon profiles drive these behavioural effects.

The Perfect Cytokine Storm: How Peripheral Immune Challenges Impact Brain Plasticity & Memory Function in Aging

Precipitous declines in cognitive function can occur in older individuals following a variety of peripheral immune insults, such as surgery, infection, injury, and unhealthy diet. Aging is associated with numerous changes to the immune system that shed some light on why this abrupt cognitive deterioration may occur. Normally, peripheral-to-brain immune signaling is tightly regulated and advantageous; communication between the two systems is bi-directional, via either humoral or neural routes. Following an immune challenge, production, secretion, and translocation of cytokines into the brain is critical to the development of adaptive sickness behaviors. However, aging is normally associated with neuroinflammatory priming, notably microglial sensitization. Microglia are the brain’s innate immune cells and become sensitized with advanced age, such that upon immune stimulation they will mount more exaggerated neuroimmune responses. The resultant elevation of pro-inflammatory cytokine expression, namely IL-1β, has profound effects on synaptic plasticity and, consequentially, cognition. In this review, we (1) investigate the processes which lead to aberrantly elevated inflammatory cytokine expression in the aged brain and (2) examine the impact of the pro-inflammatory cytokine IL-1β on brain plasticity mechanisms, including its effects on BDNF and AMPA and NMDA receptor-mediated long-term potentiation.

Relish plays a dynamic role in the niche to modulate Drosophila blood progenitor homeostasis in development and infection

Immune challenges demand the gearing up of basal hematopoiesis to combat infection. Little is known about how during development, this switch is achieved to take care of the insult. Here, we show that the hematopoietic niche of the larval lymph gland of Drosophila senses immune challenge and reacts to it quickly through the nuclear factor-κB (NF-κB), Relish, a component of the immune deficiency (Imd) pathway. During development, Relish is triggered by ecdysone signaling in the hematopoietic niche to maintain the blood progenitors. Loss of Relish causes an alteration in the cytoskeletal architecture of the niche cells in a Jun Kinase dependent manner, resulting in the trapping of Hh implicated in progenitor maintenance. Notably, during infection, downregulation of Relish in the niche tilts the maintenance program towards precocious differentiation, thereby bolstering the cellular arm of the immune response.

Large-scale deregulation of gene expression by artificial light at night in tadpoles of common toads

Artificial light at night (ALAN) affects numerous physiological and behavioural mechanisms in various species by potentially disturbing circadian timekeeping systems. Although gene-specific approaches have already shown the deleterious effect of ALAN on the circadian clock, immunity and reproduction, large-scale transcriptomic approaches with ecologically relevant light levels are still lacking to assess the global impact of ALAN on biological processes. Moreover, studies have focused mainly on variations in gene expression during the night in the presence of ALAN but never during the day. In a controlled laboratory experiment, transcriptome sequencing of Bufo bufo tadpoles revealed that ALAN affected gene expression at both night and daytime with a dose-dependent effect and globally induced a downregulation of genes. ALAN effects were detected at very low levels of illuminance (0.1 lux) and affected mainly genes related to the innate immune system and, to a lesser extend to lipid metabolism. These results indicate that a broad range of physiological pathways is impacted at the molecular level by very low levels of ALAN potentially resulting in reduced survival under environmental immune challenges.