Age matters: Differential effects of the exposure to elevated environmental temperatures on representative variables of the immune system in juvenile and adult female Japanese quail.

Several days under the influence of high environmental temperature negatively impact on some immune-related variables of poultry species. However, it is little known whether this exposure affects differentially the immune response on different life stages. This study was aimed at characterizing the immune responses of juvenile and adult female Japanese quail (Coturnix coturnix) when exposed to a cyclic chronic heat stressor. Independent sets of juvenile (24) and adult (21) female Japanese quail were bred under thermoneutral conditions or exposed to an increasing temperature from 24 °C to 34 °C, for 8 h along nine consecutive days (chronic heat stressor). The inflammatory response against a mitogen, the antibody production against a non-pathogenic antigen and the heterophil to lymphocyte (H/L) ratio were measured after the ninth day of chronic heat exposure. Adult females had a more robust inflammatory response compared to their juvenile counterpart. The inflammatory response, the production of antibodies, and the H/L ratio were suppressed by the chronic heat stressor in the juvenile females; while in their adult counterpart, the production of antibodies was not affected by the chronic heat stress. Under the exposure of high environmental temperatures, juvenile females would be more susceptible to potentially harmful pathogens that require a robust immune response, while their adult counterparts would be able to mount an optimal acquired immune response against pathogens requiring this type of response. Our findings suggest that while heat stress during breeding should be avoided in both juvenile and adult females, more precautions should be taken during early life stages.

The immune-neuroendocrine system, a key aspect of poultry welfare and resilience.

There is increasing societal concern regarding the negative impact of intensive poultry production on animal welfare, human health, and on the environment. This is leading to the inclusion of animal welfare as an imperative aspect for sustainable production. Certain environmental factors may challenge domesticated birds, resulting in poor health and welfare status. Resilience is the capacity to rapidly return to prechallenge status after coping with environmental stressors, thus resilient individuals have better chances to maintain good health and welfare. Immune-neuroendocrine system, thoroughly characterized in the domestic bird species, is the physiological scaffold for stress coping and health maintenance, influencing resilience and linking animal welfare status to these vital responses. Modern domestic bird lines have undergone specific genetic selective pressures for fast-growing, or high egg-production, leading to a diversity of birds that differ in their coping capacities and resilience. Deepening the knowledge on pro/anti-inflammatory milieus, humoral/cell-mediated immune responses, hormonal regulations, intestinal microbial communities and mediators that define particular immune and neuroendocrine configurations will shed light on coping strategies at the individual and population level. The understanding of the profiles leading to differential coping and resilience potential will be highly relevant for improving bird health and welfare in a wider range of challenging scenarios and, therefore, crucial to scientifically tackle long term sustainability.

Network Analysis of Inflammatory Bowel Disease Research: Towards the Interactome.

BACKGROUND AND AIMS: Modern views accept that inflammatory bowel diseases [IBD] emerge from complex interactions among the multiple components of a biological network known as the 'IBD interactome'. These diverse components belong to different functional levels including cells, molecules, genes and biological processes. This diversity can make it difficult to integrate available empirical information from human patients into a collective view of aetiopathogenesis, a necessary step to understand the interactome. Herein, we quantitatively analyse how the representativeness of components involved in human IBD and their relationships ha ve changed over time. METHODS: A bibliographic search in PubMed retrieved 25 971 abstracts of experimental studies on IBD in humans, published between 1990 and 2020. Abstracts were scanned automatically for 1218 IBD interactome components proposed in recent reviews. The resulting databases are freely available and were visualized as networks indicating the frequency at which different components are referenced together within each abstract. RESULTS: As expected, over time there was an increase in components added to the IBD network and heightened connectivity within and across functional levels. However, certain components were consistently studied together, forming preserved motifs in the networks. These overrepresented and highly linked components reflect main 'hypotheses' in IBD research in humans. Interestingly, 82% of the components cited in reviews were absent or showed low frequency, suggesting that many aspects of the proposed IBD interactome still have weak experimental support in humans. CONCLUSIONS: A reductionist and fragmented approach to the study of IBD has prevailed in previous decades, highlighting the importance of transitioning towards a more integrated interactome framework.

Modulating offspring responses: concerted effects of stress and immunogenic challenge in the parental generation.

The perception, processing and response to environmental challenges involves the activation of the immuno-neuroendocrine (INE) interplay. Concerted environmental challenges might induce trade-off when resource allocation to one trait occurs at the expense of another, also producing potential transgenerational effects in the offspring. We evaluated whether concerted challenges, in the form of an immune inoculum against inactivated Salmonella enteritidis (immune challenge, ICH) and a chronic heat stress (CHS) exposure on adult Japanese quail, modulate the INE responses of the parental generation and their offspring. Adults were inoculated and later exposed to a CHS along nine consecutive days. For the last 5 days of the CHS, eggs were collected for incubation. Chicks were identified according to their parental treatments and remained undisturbed. Induced inflammatory response, heterophil/lymphocyte (H/L) ratio and specific humoral response against sheep red blood cells (SRBC) were evaluated in both generations. Regardless of the ICH, stressed adults showed a reduced inflammatory response and an elevated H/L ratio compared with controls. In offspring, the inflammatory response was elevated and the specific SRBC antibody titres were diminished in those chicks prenatally exposed to CHS, regardless of the ICH. No differences were found in the H/L ratio of the offspring. Together, our results suggest that CHS exposure influences the INE interplay of adult quail, establishing trade-offs within their immune system. Moreover, CHS not only affected parental INE responses but also modulated their offspring INE responses, probably affecting their potential to respond to future challenges. The adaptability of the developmental programming of offspring would depend on the environment encountered.

A selective window after the food-intake period favors tolerance induction in mesenteric lymph nodes.

Biological rhythms are periodic oscillations that occur in the physiology of the organism and the cells. The rhythms of the immune system are strictly regulated and the circadian alteration seems to have serious consequences. Even so, it is not clear how the immune cells of the intestinal mucosa synchronize with the external environment. Besides, little is known about the way in which biological rhythms affect the critical functions of intestinal immunity, such as oral tolerance. We studied fluctuations in the relevant parameters of intestinal immunity at four different times throughout the day. By using multivariate statistical tools, we found that these oscillations represent at least three different time frames with different conditions for tolerance induction that are altered in Per2ko mice lacking one of the clock genes. Our results allowed us to characterize a window in the final stage of the dark phase that promotes the induction of specific regulatory populations and favors its location in the lamina propria. We show here that, at the end of the intake, the entry of luminal antigens, soluble factors, and leukocyte populations converge in the mesenteric lymph nodes (MLN) and display the greatest potential of the tolerogenic machinery.

Soy genistein administered in soluble chitosan microcapsules maintains antioxidant activity and limits intestinal inflammation.

We used water-soluble Chitosan obtained by Maillard reaction with glucosamine to microencapsulate soy genistein (Ge) and preserve its biological activity for oral administration. Release of Ge was pH dependent with a super Case II mechanism at pH 1.2 and an anomalous transport with non-Fickian kinetics at pH 6.8. Microencapsulated Ge retained its antioxidant properties in vitro and its daily administration to mice attenuated clinical signs of acute colitis, limited inflammatory reaction and reduced oxidative stress and tissue injury as well. Remarkably, after feeding microencapsulated Ge the production of IL-10 in colonic tissue was restored to levels of untreated controls. According to statistical multivariate analysis, this cytokine was the parameter with the highest influence on the inflammatory/oxidative status. Microencapsulation of Ge with derivatized Chitosan becomes an interesting alternative to develop therapeutic approaches for oxidative inflammatory diseases; our findings suggest that the soy isoflavone could be incorporated into any functional food for application in intestinal inflammation.

Stress Induced Polarization of Immune-Neuroendocrine Phenotypes in Gallus gallus.

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals' interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.

Immune neuroendocrine phenotypes in Coturnix coturnix: do avian species show LEWIS/FISCHER-like profiles?

Immunoneuroendocrinology studies have identified conserved communicational paths in birds and mammals, e.g. the Hypothalamus-Pituitary-Adrenal axis with anti-inflammatory activity mediated by glucocorticoids. Immune neuroendocrine phenotypes (INPs) have been proposed for mammals implying the categorization of a population in subgroups underlying divergent immune-neuroendocrine interactions. These phenotypes were studied in the context of the LEWIS/FISCHER paradigm (rats expressing high or low pro-inflammatory profiles, respectively). Although avian species have some common immunological mechanisms with mammals, they have also evolved some distinct strategies and, until now, it has not been studied whether birds may also share with mammals similar INPs. Based on corticosterone levels we determined the existence of two divergent groups in Coturnix coturnix that also differed in other immune-neuroendocrine responses. Quail with lowest corticosterone showed higher lymphoproliferative and antibody responses, interferon-γ and interleukin-1ß mRNA expression levels and lower frequencies of leukocyte subpopulations distribution and interleukin-13 levels, than their higher corticosterone counterparts. Results suggest the existence of INPs in birds, comparable to mammalian LEWIS/FISCHER profiles, where basal corticosterone also underlies responses of comparable variables associated to the phenotypes. Concluding, INP may not be a mammalian distinct feature, leading to discuss whether these profiles represent a parallel phenomenon evolved in birds and mammals, or a common feature inherited from a reptilian ancestor millions of years ago.