Diet modulates strongyle infection and microbiota in the large intestine of horses.

The use of anthelminthic drugs has several drawbacks, including the selection of resistant parasite strains. Alternative avenues to mitigate the negative effects of helminth infection involve dietary interventions that might affect resistance and/or tolerance by improving host immunity, modulating the microbiota, or exerting direct anthelmintic effects. The aim of this study was to assess the impact of diet on strongyle infection in horses, specifically through immune-mediated, microbiota-mediated, or direct anthelmintic effects. Horses that were naturally infected with strongyles were fed either a high-fiber or high-starch diet, supplemented with either polyphenol-rich pellets (dehydrated sainfoin) or control pellets (sunflower and hay). When horses were fed a high-starch diet, they excreted more strongyle eggs. Adding sainfoin in the high-starch diet reduced egg excretion. Additionally, sainfoin decreased larval motility whatever the diet. Moreover, the high-starch diet led to a lower fecal bacterial diversity, structural differences in fecal microbiota, lower fecal pH, lower blood acetate, and lower hematocrit compared to the high-fiber diet. Circulating levels of Th1 and Th2 cytokines, lipopolysaccharides, procalcitonin, and white blood cells proportions did not differ between diets. Overall, this study highlights the role of dietary manipulations as an alternative strategy to mitigate the effect of helminth infection and suggests that, in addition to the direct effects, changes in the intestinal ecosystem are the possible underlying mechanism.

Inclusion of Sainfoin in the Diet Might Alter Strongyle Infection in Naturally Infected Horses.

It is increasingly difficult to control equine strongyles with synthetic drugs, as resistance is commonly observed. Here, we investigated the possible anthelmintic effect of sainfoin (Onobrychis viciifolia), a polyphenol-rich legume, in naturally infected horses. On Day 0 (D0), 17 horses were allocated to three different homogenous groups in terms of fecal egg count (FEC): the control group (CONT) received a diet composed on a DM basis of 83% hay and 17% wheat bran, while in the sainfoin 1 (SF1) and sainfoin 2 (SF2) groups, half or all wheat bran, respectively, was replaced by dehydrated sainfoin pellets. The infection dynamics were monitored by weekly FEC, from D0 to D84. On D28, all horses were treated with fenbendazole. Larval motility was assessed from coprocultures at D0, D28, D56 and D84. Horses in Group SF2 had lower FEC from D7 to D28. After fenbendazole treatment, no effect of the diet was measured on FEC. Both before and after anthelmintic treatment, larvae from horses consuming sainfoin were less motile than larvae from the CONT group. These results suggest that sainfoin has an in vivo anthelmintic activity in naturally infected horses, although this effect appears to be context-dependent.

Explaining among-country variation in COVID-19 case fatality rate.

While the epidemic of SARS-CoV-2 has spread worldwide, there is much concern over the mortality rate that the infection induces. Available data suggest that COVID-19 case fatality rate had varied temporally (as the epidemic has progressed) and spatially (among countries). Here, we attempted to identify key factors possibly explaining the variability in case fatality rate across countries. We used data on the temporal trajectory of case fatality rate provided by the European Center for Disease Prevention and Control, and country-specific data on different metrics describing the incidence of known comorbidity factors associated with an increased risk of COVID-19 mortality at the individual level. We also compiled data on demography, economy and political regimes for each country. We found that temporal trajectories of case fatality rate greatly vary among countries. We found several factors associated with temporal changes in case fatality rate both among variables describing comorbidity risk and demographic, economic and political variables. In particular, countries with the highest values of DALYs lost to cardiovascular, cancer and chronic respiratory diseases had the highest values of COVID-19 CFR. CFR was also positively associated with the death rate due to smoking in people over 70 years. Interestingly, CFR was negatively associated with share of death due to lower respiratory infections. Among the demographic, economic and political variables, CFR was positively associated with share of the population over 70, GDP per capita, and level of democracy, while it was negatively associated with number of hospital beds ×1000. Overall, these results emphasize the role of comorbidity and socio-economic factors as possible drivers of COVID-19 case fatality rate at the population level.

Development and optimization of a hybridization technique to type the classical class I and class II B genes of the chicken MHC.

The classical class I and class II molecules of the major histocompatibility complex (MHC) play crucial roles in immune responses to infectious pathogens and vaccines as well as being important for autoimmunity, allergy, cancer and reproduction. These classical MHC genes are the most polymorphic known, with roughly 10,000 alleles in humans. In chickens, the MHC (also known as the BF-BL region) determines decisive resistance and susceptibility to infectious pathogens, but relatively few MHC alleles and haplotypes have been described in any detail. We describe a typing protocol for classical chicken class I (BF) and class II B (BLB) genes based on a hybridization method called reference strand-mediated conformational analysis (RSCA). We optimize the various steps, validate the analysis using well-characterized chicken MHC haplotypes, apply the system to type some experimental lines and discover a new chicken class I allele. This work establishes a basis for typing the MHC genes of chickens worldwide and provides an opportunity to correlate with microsatellite and with single nucleotide polymorphism (SNP) typing for approaches involving imputation.

The macroecology of cancer incidences in humans is associated with large-scale assemblages of endemic infections.

It is now well supported that 20% of human cancers have an infectious causation (i.e., oncogenic agents). Accumulating evidence suggests that aside from this direct role, other infectious agents may also indirectly affect cancer epidemiology through interactions with the oncogenic agents within the wider infection community. Here, we address this hypothesis via analysis of large-scale global data to identify associations between human cancer incidence and assemblages of neglected infectious agents. We focus on a gradient of three widely-distributed cancers with an infectious cause: bladder (~2% of recorded cancer cases are due to Shistosoma haematobium), liver (~60% consecutive to Hepatitis B and C infection) and stomach (Helicobacter pylori is associated with ~70% of cases). We analyzed countries in tropical and temperate regions separately, and controlled for many confounding social and economic variables. First, we found that particular assemblages of bacteria are associated with bladder cancer incidences. Second, we observed a specific and robust association between helminths and liver cancer incidences in both biomes. Third, we show that certain assemblages of viruses may facilitate stomach cancer in tropical area, while others protect against its development in temperate countries. Finally, we discuss the implications of our results in terms of cancer prevention and highlight the necessity to consider neglected diseases, especially in tropics, to adapt public health strategies against infectious diseases and cancer.

Infections and cancer: the "fifty shades of immunity" hypothesis.

BACKGROUND: Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction. DISCUSSION: Lost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways - from functional aspects to evolutionary considerations such as modernity mismatches - by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels. Infectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase our knowledge about immune interactions between infections and cancer.

Cancer: A disease at the crossroads of trade-offs.

Central to evolutionary theory is the idea that living organisms face phenotypic and/or genetic trade-offs when allocating resources to competing life-history demands, such as growth, survival, and reproduction. These trade-offs are increasingly considered to be crucial to further our understanding of cancer. First, evidences suggest that neoplastic cells, as any living entities subject to natural selection, are governed by trade-offs such as between survival and proliferation. Second, selection might also have shaped trade-offs at the organismal level, especially regarding protective mechanisms against cancer. Cancer can also emerge as a consequence of additional trade-offs in organisms (e.g., eco-immunological trade-offs). Here, we review the wide range of trade-offs that occur at different scales and their relevance for understanding cancer dynamics. We also discuss how acknowledging these phenomena, in light of human evolutionary history, may suggest new guidelines for preventive and therapeutic strategies.

Interactions between immune challenges and cancer cells proliferation: timing does matter!

The immune system is a key component of malignant cell control and it is also involved in the elimination of pathogens that threaten the host. Despite our body is permanently exposed to a myriad of pathogens, the interference of such infections with the immune responses against cancer has been poorly investigated. Through a mathematical model, we show that the frequency, the duration and the action (positive or negative) of immune challenges may significantly impact tumor proliferation. First, we observe that a long immunosuppressive challenge increases accumulation of cancerous cells only if it occurs 14 years after the beginning of immunosenescence. However, short immune challenges result in an even greater accumulation of cancerous cells for the same total duration of immunosuppression. Finally, we show that short challenges of immune activation could lead to a slightly decrease in cancerous cell accumulation compared to a long one. Our results predict that frequent and acute immune challenges could have a different and in some extent higher impact on cancer risk than persistent ones even they have been much less studied in cancer epidemiology. These results are discussed regarding the existing empirical evidences and we suggest potential novel indirect role of infectious diseases on cancer incidence which should be investigated to improve prevention strategies against cancer.

Correlational selection on pro- and anti-inflammatory effectors.

Parasites impose a permanent threat for hosts. As a consequence, immune defenses are important for host fitness. However, the immune response can also produce self-damage and impair host fitness if not properly regulated. Effectors that up- and downregulate the immune response should, therefore, evolve in concert, and be under the action of correlational selection. To address this issue, we assessed the shape of the selection operating on pro- and anti-inflammatory effectors following an inflammatory challenge in laboratory mice.We found that selection acts on the combination of these two traits as individuals that produced large amount of pro-inflammatory cytokines could achieve relatively high fitness (survival) only if also producing a large amount of anti-inflammatory effectors. To our knowledge, this is the first study providing evidence for correlational selection on immunity.

Do carotenoid-based sexual traits signal the availability of non-pigmentary antioxidants?

Carotenoid-based signals are thought to be indicators of male quality because they must be obtained from the diet and might thus indicate the ability of individuals to gather high-quality food. However, carotenoids are also known to have important physiological functions as immunoenhancers and antioxidants, and, as such, carotenoid-based sexual traits have also been suggested to reflect the health and antioxidant status of their bearers. This last idea is based on the hypothesis that carotenoids that are allocated to sexual signals are no longer available for the detoxification system. Recently, this hypothesis has been challenged on the grounds that the antioxidant activity is not the main biological role of carotenoids. Instead, carotenoid-based sexual traits might signal the availability of other non-pigmentary antioxidant molecules that might protect carotenoids from free radical attacks and make them available for sexual advertisements. We tested this hypothesis in the zebra finch, a passerine species with a carotenoid-based signal: the colour of the bill. We simultaneously manipulated the availability of carotenoids and of a non-pigmentary antioxidant (melatonin) in the drinking water. If the antioxidant properties of melatonin protect carotenoids from oxidation, we predict that birds supplemented with melatonin should have redder bills than birds not supplemented with melatonin, and that birds supplemented with carotenoids and melatonin should have redder bills than birds supplemented with carotenoids alone. Our findings are in agreement with these predictions since carotenoid and melatonin supplementation had an additive effect on bill colour. To our knowledge this is the first experimental evidence that a non-pigmentary antioxidant enhances the expression of a carotenoid-based sexual trait.

An experimental test of the dose-dependent effect of carotenoids and immune activation on sexual signals and antioxidant activity.

Carotenoid-based sexual traits are thought to be reliable indicators of male quality because they might be scarce and therefore might indicate the ability of males to gather high-quality food and because they are involved in important physiological functions (as immune enhancers and antioxidants). We performed an experiment where male and female zebra finches (Taeniopygia guttata) were provided with increasing carotenoid doses in the drinking water during 4 weeks (bill color of this species is a carotenoid-based sexual signal). Simultaneously, birds were split into two groups: one receiving weekly injections of Escherichia coli lipopolysaccharide in order to activate the immune system, the other being injected with the same volume of phosphate buffered saline. We assessed how carotenoid availability and immune activation affected the amount of circulating plasma carotenoids, the beak color, and the antioxidant defenses (assessed as the resistance of red blood cells to a controlled free radical attack). Carotenoid availability affected the amount of circulating carotenoids and beak color; both variables reached a plateau at the highest carotenoid doses. Immune activation diverted carotenoids from plasma, and this in turn affected the expression of the sexual trait. Finally, we found a positive correlation between the change in circulating carotenoids and antioxidant defenses. These results support the idea that carotenoids have important physiological properties that ensure the honesty of carotenoid-based sexual traits.