The Role of Microbiome and Genotype in Daphnia magna upon Parasite Re-Exposure.

Recently, it has been shown that the community of gut microorganisms plays a crucial role in host performance with respect to parasite tolerance. Knowledge, however, is lacking on the role of the gut microbiome in mediating host tolerance after parasite re-exposure, especially considering multiple parasite infections. We here aimed to fill this knowledge gap by studying the role of the gut microbiome on tolerance in Daphnia magna upon multiple parasite species re-exposure. Additionally, we investigated the role of the host genotype in the interaction between the gut microbiome and the host phenotypic performance. A microbiome transplant experiment was performed in which three germ-free D. magna genotypes were exposed to a gut microbial inoculum and a parasite community treatment. The gut microbiome inocula were pre-exposed to the same parasite communities or a control treatment. Daphnia performance was monitored, and amplicon sequencing was performed to characterize the gut microbial community. Our experimental results showed that the gut microbiome plays no role in Daphnia tolerance upon parasite re-exposure. We did, however, find a main effect of the gut microbiome on Daphnia body size reflecting parasite specific responses. Our results also showed that it is rather the Daphnia genotype, and not the gut microbiome, that affected parasite-induced host mortality. Additionally, we found a role of the genotype in structuring the gut microbial community, both in alpha diversity as in the microbial composition.

Jackdaw nestlings rapidly increase innate immune function during the nestling phase but no evidence for a trade-off with growth.

Although animals are born with a protective immune system, even the innate immune system is under development from birth to adulthood and this development may be affected by sex and growth. However, most knowledge comes from captive animals or long-lived slow growing species. Moreover, little is known about how innate immune function, the important first line of defence, develops during early life in fast-growing animals such as free-living passerines. We studied development of innate baseline immune function in nestlings of free-living jackdaws Corvus monedula. We measured four immune parameters (hemolysis, hemagglutination, bacterial-killing capacity, haptoglobin concentration) and structural body size (body mass, wing length, tarsus length) at day 12 and day 29 post-hatching. We found that three out of four immune parameters (hemolysis, hemagglutination, bacterial-killing capacity) substantially increased with nestling age and had roughly reached adult levels shortly prior to fledging. We found little differences in immune development between males and females despite them differing in structural development. We also found no evidence that the nestlings traded off immune development with growth. That nestlings rapidly increase innate baseline immune function during early life and similarly in males and females indicates the importance of a well-functioning immune system already during the nestling phase.

Costs of immune responses are related to host body size and lifespan.

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise, body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.

Associations of A-FABP with Anthropometric and Metabolic Indices and Inflammatory Cytokines in Obese Patients with Newly Diagnosed Type 2 Diabetes.

The study aimed to evaluate the relationship between anthropometric and metabolic indices, inflammatory cytokines, and adipocyte fatty acid-binding protein (A-FABP) in obese patients with newly diagnosed type 2 diabetes. The study included 48 nonobese subjects with newly diagnosed type 2 diabetes, 42 obese subjects with newly diagnosed type 2 diabetes, 30 simple obese subjects, and 30 matched normal subjects. Serum A-FABP was assessed by enzyme-linked immunosorbent assay. Pearson's correlations and multiple linear regression stepwise analysis were used to analyze correlations of A-FABP with anthropometric and metabolic indices and inflammatory cytokines. Obese subjects with newly diagnosed type 2 diabetes had elevated A-FABP compared to normal control, nondiabetic obese patients, and nonobese diabetic patients. A-FABP was significantly correlated with glycated hemoglobin A1C (HbA1C), BMI, triglyceride, Homeostasis Model Assessment Index (HOMA-IR), waist hip rate, C-reactive protein, IL-6, and HDL-C in obese subjects with type 2 diabetes. In multiple linear regression stepwise analysis, BMI, HbA1C, and HOMA-IR were significantly independent determinants for A-FABP. BMI, HbA1C, and HOMA-IR are independently associated with A-FABP in obese subjects with newly diagnosed type 2 diabetes. A-FABP may be related to insulin resistance and inflammation in type 2 diabetes and concomitant obesity.

The effects of temperature and body size on immunological development and responsiveness in juvenile shortnose sturgeon (Acipenser brevirostrum).

Sturgeon are an important evolutionary taxa of which little is known regarding their responses to environmental factors. Water temperature strongly influences growth in fish; however, its effect on sturgeon immune responses is unknown. The objective of this study was to assess how 2 different temperatures affect immune responses in shortnose sturgeon (Acipenser brevirostrum) relevant immune organs such as the meningeal myeloid tissue, spleen, thymus and skin. These responses were studied in 2 different sizes of same age juvenile sturgeon kept at either 11 °C or 20 °C (4 treatment groups), before and after exposure to an ectoparasitic copepod (Dichelesthium oblongum). Based on a differential cell count, temperature was found to strongly influence immune cell production in the meningeal myeloid tissue, regardless of the fish sizes considered. Morphometric analysis of splenic white pulp showed a transient response to temperature. There were no differences between the groups in the morphometric analysis of thymus size. Splenic IRF-1 and IRF-2 had similar expression profiles, significantly higher in fish kept at 20 °C for the first 6 weeks of the study but not by 14 weeks. In the skin, IRF-1 was significantly higher in the fish kept at 11 °C over the first 6 weeks of the study. IRF-2 had a similar profile but there were no differences between the groups by the end of the trial. In conclusion, higher water temperatures (up to 20 °C) may have beneficial effects in maximizing growth and improving immunological capacity, regardless of the fish sizes considered in this study.

Impact of total-body irradiation on the response to a live bacterial challenge.

PURPOSE: Concern regarding radiation effects on human health continues to increase worldwide. Given that infection is a major cause of morbidity and mortality after exposure, the aim of this study was to evaluate decrements in immune cell populations using a mammalian model subjected to a live bacterial infection. MATERIALS AND METHODS: C57BL/6 mice were exposed to total-body irradiation (TBI) with 3 Gy protons (70 cGy/min). One, 2, 4, 8 or 16 days later, subsets of mice were injected intraperitoneally with live Escherichia coli [055:K59(B5)]. Control groups received no radiation and vehicle (no bacteria). The mice were euthanized for analyses 90-120 min after injection of the bacteria. RESULTS: There were no unexpected effects of radiation or E. coli alone. Despite dramatic radiation-induced decreases in all leukocyte populations in both the blood and spleen, irradiated mice were still able to respond to an immune challenge based on capacity to generate an oxidative burst and secrete inflammatory cytokines, i.e., tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). However, these responses were generally elevated above control values. CONCLUSIONS: Together, these results suggest the possibility for enhanced inflammation-associated tissue injury and increased risk for chronic inflammation.

Dynamics of PHA-induced immune response and plasma carotenoids in birds: should we have a closer look?

Allocation trade-offs of limited resources are thought to ensure the honesty of sexual signals and are often studied using controlled immune challenges. One such trade-off between immunity and ornaments is that involving carotenoids. Phytohemagglutinin (PHA)-induced immune response is a widely used immune challenge, yet more details on the underlying physiological mechanisms and potential costs are needed. We investigated the temporal dynamics of PHA-induced immune response and associated changes in blood carotenoids, body mass and a carotenoid-based coloured signal. We found variation in individual response patterns to PHA after peak swelling was reached, with birds showing either a rapid or a slow subsequent decrease in swelling, suggesting variation in the duration of the immune response and/or inflammation. Body mass did not affect immune response. Plasma carotenoids followed a transient decrease closely matching the dynamics of the swelling. The peak of the immune response was negatively related to initial plasma carotenoid levels and positively correlated to the relative decrease in plasma carotenoids. Individual variation in duration of the swelling could be partly explained by plasma carotenoids; high initial carotenoid levels were associated with a slower decrease of the swelling. These contradictory effects of carotenoids suggest a complex role in the immune response. Bill colour was positively correlated to initial plasma carotenoid concentration but it did not predict or change as a consequence of immune response to PHA. Bill colour thus reflects medium- or long-term quality rather than immediate quality. Taking into account the dynamics of the immune response and that of associated physiological parameters would thus yield new insights into our interpretation of variation in PHA response.

Genetic syndromic immunodeficiencies with antibody defects.

This article reviews the major syndromic immunodeficiencies with significant antibody defects, many of which may require intravenous immunogammaglobulin therapy. The authors define syndromic immunodeficiency as an illness associated with a characteristic group of phenotypic abnormalities or laboratory features that comprise a recognizable syndrome. Many are familial with a defined inheritance pattern. Immunodeficiency may not be a major part of the illness and may not be present in all patients; thus, these conditions differ from primary immunodeficiency syndromes, in which immune abnormalities are a consistent and prominent feature of their disease.

The stimulation of immune defence accelerates development in the red flour beetle (Tribolium castaneum).

The timing of the transition between life stages is of key importance for an organism. Depending on the environmental conditions, maturing earlier at a smaller size or maturing later at a larger size can be advantageous for fitness. Exposure to parasites and subsequent immune activation may lead to alterations in development. Immune defence often comes at a cost, such as energy drain towards immune function, which is likely to delay development. On the other hand, animals may react to an anticipated risk of infection with a phenotypically plastic shift in life history, which may more likely lead to accelerated development and earlier maturation. We tested these alternatives in the red flour beetle, Tribolium castaneum. Young larvae were exposed to a non-infectious immune challenge with heat-killed bacteria (either Escherichia coli or Bacillus thuringiensis) and they were followed up for their development, survival, adult size and reproduction. We found that animals that had experienced a bacterial challenge developed into adults earlier than sham-treated beetles, while they did not differ significantly in survival or adult size. Beetles exposed to E. coli produced fewer offspring, while exposure to B. thuringiensis did not affect offspring number. Taken together, our results indicate that T. castaneum is able to speed up its development when facing a risk of infection.

Dynamic expression of immune response genes in the sea bass, Dicentrarchus labrax, experimentally infected with the monogenean Diplectanum aequans.

The sea bass, Dicentrarchus labrax, is one of the most extensively farmed marine fishes in the Mediterranean. Under the high-density condition common in aquaculture, the monogenean gill parasite Diplectanum aequans can cause significant economic losses. This study used real-time quantitative PCR to investigate the dynamic expression of immune response genes in sea bass infected with Diplectanum aequans. The target genes, interleukin-1 (IL-1beta, transforming growth factor (TGF-beta and T-cell receptor (TCR-beta), were studied in the gills and spleen of the sea bass from the first day of infection until thirty days post- infection. Our results showed that there was an increase in IL-1beta gene expression in the spleen and gills and in TGF-beta gene expression in the gills of infected fish. These results show that parasitic infection induced a local inflammatory reaction and that reaction was restricted to the site of infection. Finally, the absence of relationship between TCR-beta expression and the parasitic infection suggests that the adaptive immune system is not involved in the response against this parasite.

Immune defense of ants is associated with changes in habitat characteristics.

Although the immune functions of insects are known to correlate with body condition and food resources, the association between habitat structure and immune function is still largely unknown. We studied the effects of forest clear-cutting on encapsulation rate in gynes and workers in the forest-dwelling ant Formica aquilonia. Forest logging resulted in disturbed immunity in workers and gynes. Logging enhanced encapsulation reaction in gynes, whereas decreased that of workers. In gynes, there was a likely trade-off between growth and immune function that was apparent in terms of different investment in size and immune function in different habitats. In workers, however, such associations were not found. The results indicate that, because of disturbed immunity, environmental stress may increase susceptibility of wood ants to diseases and parasites in disturbed habitats.

Intestinal pH profile in rainbow trout Oncorhynchus mykiss and microhabitat preference of the flagellate Spironucleus salmonis (Diplomonadida).

In farmed rainbow trout Oncorhynchus mykiss, the flagellate Spironucleus salmonis (Diplomonadida) is often found in the pyloric region of the intestine. While previous in vitro studies report a pH of 7.5 to 8.0 as optimal for presumed S. salmonis, no previous in vivo studies have investigated the relationship between pH and microhabitat preference. Therefore, in 698 rainbow trout (75% were 5 to 6 mo old juveniles, 10 to 20 cm total length), we recorded occurrence and density of S. salmonis, and pH, in the pyloric, anterior, middle, and posterior intestine. There were no significant differences in total length or weight between infected and uninfected fish. S. salmonis preferred the pyloric region, with occurrence and density decreasing significantly from pyloric to posterior regions. In infected fish, pH in pyloric (6.8 to 7.9, mean 7.3) and posterior regions (6.5 to 8.0, mean 7.1) was significantly lower than in anterior (6.5 to 8.5, mean 7.7) and middle (6.8 to 8.2, mean 7.7) regions; in uninfected fish, the pH profile was similar. At the individual level, 90 % of infected fish and 79% of uninfected fish showed this pH profile. In the pyloric region, pH was not significantly different among uninfected fish, and fish with light, moderate, or heavy infections. Our in vivo study suggests the optimal pH for S. salmonis is between 7.1 and 7.5, possibly close to 7.3 (the mean in pyloric region of infected fish). We conclude that while the presence of S. salmonis reflected tolerable pH, density of infection was not correlated with pH, and thus a causal relationship between microhabitat preference and pH is unlikely.

Association between indices of body mass and antibody titres to heat-shock protein-60, -65 and -70 in healthy Caucasians.

We have previously shown that antibody titres to several heat-shock proteins (Hsps) are elevated in dyslipidaemic patients and subjects with established vascular disease. Obesity is known to be associated with raised serum inflammatory markers suggesting a state of heightened immune activation. Hence, we have investigated the association between indices of obesity and several Hsp antibody titres in healthy subjects. Subjects (n=170) were recruited from among employees at the University of Surrey and the Royal Surrey County Hospital, Guildford, UK. Of these subjects, 35 were obese with a body mass index (BMI)>/=30 kg/m(2) (19 male and 16 female subjects), 58 were overweight with 30>BMI>/=25 kg/m(2) (36 male and 22 female subjects) and 77 were of a normal weight with BMI<25 kg/m(2) (31 male and 46 female subjects). Overall, obese subjects had significantly higher plasma anti-Hsp-60 (P<0.001), anti-Hsp-65 (P<0.05) and anti-Hsp-70 (P<0.05) compared with overweight and normal weight subjects.

Sexual comparisons in immune ability, survival and parasite intensity in two damselfly species.

Recent evolutionary studies have suggested that females have a more robust immune system than males. Using two damselfly species (Hetaerina americana and Argia tezpi), we tested if females produced higher immune responses (as phenoloxidase and hydrolytic enzymes), had a higher survival (using a nylon implant inserted in the abdomen and measuring survival after 24h) and fewer parasites (gregarines and water mites) than males. We also tested whether immune differences should emerge in different body areas (thorax vs. abdomen) within each sex with the prediction that only females will differ with the abdomen having a higher immune response than their thorax since the former area, for ecological and physiological reasons, may be a target zone for increased immune investment. Animals were adults of approximately the same age. In both species, females were more immunocompetent than males, but only in H. americana females were immune responses greater in the abdomen than in the thorax. However, there were no differences in survival and parasite intensity or the probability of being parasitised between the sexes in either of the two species. Thus, this study lends partial support to the principle that females are better at defending than males despite the null difference in parasitism and survival.

Infections in infancy and the presence of antinuclear antibodies in adult life.

There has been limited success defining environmental factors important to the development of connective tissue diseases such as systemic lupus erythematosus (SLE). Recent work has suggested that the perinatal environment may be important. To investigate this we measured antinuclear antibodies (ANA) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with ANA positivity in adult life. Included in our investigation were 1334 individuals (668 men, 666 women) from the Hertfordshire cohort study. ANA was measured using an ANA ELISA and confirmed using immunofluorescence. We investigated associations between the presence of ANA and early growth and infectious exposure in infancy in men and women combined, but with adjustment for gender throughout. A positive ANA was present in 73 (10.9%) of men and 81 (12.2%) women. Of these, 26 women and 14 men were positive using IF on HEP2 cells. Sharing a bedroom during childhood was associated with a higher risk of being ANA positive (odds ratio (OR), 1.42, 95% confidence interval (CI) 1.00-2.01, P = 0.05). A record of diarrhoeal illness (OR 2.12 95% CI 1.07, 4.23, P = 0.03) and rubella or mumps during the first year of life (OR 16.12, 95% CI 2.92, 88.94, P = 0.001) was also significantly associated with ANA in adult life. Higher ANA titres by Inova ELISA were associated with infections in the first year of life from mumps (2.74-fold higher, 95% CI 0.98, 7.64, P = 0.05) and rubella (3.90-fold higher, 95% CI 1.89, 8.04, P < 0.001). In addition, higher ANA titres were also associated with mumps (1.26-fold higher, 95% CI 1.02, 1.56, P = 0.03) between one and five years of age. Our results suggest that a developing immune system exposed to increased infection is more likely to produce ANA in adult life and perhaps begin the pathological process that leads to SLE.