Transgenerational Effects of Maternal Immune Activation on Specific Antibody Responses in Layer Chickens.

Activation of the maternal immune system may affect innate and adaptive immune responses in the next generation and may therefore have implications for vaccine efficacy and dietary immune modulation by feed additives. However, transgenerational effects on immune responses in chickens have been investigated to a limited extend. The present study investigated effects of intratracheal (i.t) specific and aspecific immune activation of laying hens on specific antibody production in the next generation. In two experiments laying hens received intratracheally an immune stimulus with human serum albumin (HuSA) or lipopolysaccharide (LPS). In experiment 1, hatchlings of the immune activated hens were at 4 weeks i.t. immunized with HuSA or HuSA+LPS. Maternal immune activation with LPS increased HuSA specific IgY and IgM responses in offspring. These results suggest a transgenerational effect of the maternal immune system on the specific antibody response in the next generation. In experiment 2 hatchlings received either ß-glucan-enriched feed or control feed and were i.t. immunized with HuSA. Maternal immune activation with LPS decreased IgY anti-HuSA responses after HuSA immunization within hatchlings that received ß-glucan enriched feed. The results of Experiment 2 suggest a transgenerational link between the innate immune system of mother and specific antibody responses in offspring. Despite variabilities in the outcomes of the two experiments, the observations of both suggest a link between the maternal innate immune system and the immune system of the offspring. Furthermore, our results may imply that maternal activation of the innate immune system can influence immune modulating dietary interventions and vaccine strategies in the next generation.

Transgenerational effects of innate immune activation in broiler breeders on growth performance and immune responsiveness.

The impact of transgenerational effects on growth performance and immunity has not yet been studied extensively within the poultry husbandry sector. An important factor is the impact of the hens on the physical well-being and fitness to the environment of the offspring. This study is the first to investigate the effect of stimulating the maternal innate immune system with lipopolysaccharides (LPS) or ß-glucan on growth performance and immune responses in the next generation. Transgenerational effects and consequences of these maternal treatments were further examined using a necrotic enteritis (NE) challenge model in the offspring. We show that offspring of LPS-treated broiler breeders have a higher feed efficiency from 14 to 21 days of age, that is, the period just after the NE challenge. Moreover, more broiler chickens with intestinal lesions after the NE challenge were found in the offspring of the LPS-treated broiler breeders. Both the LPS and ß-glucan maternal treatments resulted in transgenerational effects on blood-derived monocytes by showing a tendency of decreased IL1ß mRNA levels after ex vivo LPS stimulation. These data are a first indication that broiler breeder hens can affect immune responsiveness and feeding efficiency of their offspring in a transgenerational manner.

Innate immune training and metabolic reprogramming in primary monocytes of broiler and laying hens.

Recently, we have reported trained innate immunity in laying chicken monocytes. In the present study, we further investigated trained innate immunity of monocytes in layers and broilers. Monocytes of both breeds isolated from blood were trained in vitro with ß-glucan, rec-chicken IL-4 or a combination of both, and restimulated with lipopolysaccharide (LPS), after which inflammation and metabolism-related responses were measured. Training of laying and broiler hen monocytes resulted in increased mRNA levels of IL-1ß, iNOS and HIF-1α, but enhanced surface expression of CD40 and NO production was only observed in layers. Our in vitro study demonstrates that monocytes from different genetic backgrounds can be trained. However, the observed differences suggest a differential effect on immune functionality associated with innate training. Whether these differences in immune functions between layers and broilers have effect on disease resistance remains to be elucidated.

Training of Primary Chicken Monocytes Results in Enhanced Pro-Inflammatory Responses.

Beta-glucan-stimulated mammalian myeloid cells, such as macrophages, show an increased responsiveness to secondary stimulation in a nonspecific manner. This phenomenon is known as trained innate immunity and is important to prevent reinfections. Trained innate immunity seems to be an evolutionary conserved phenomenon among plants, invertebrates and mammalian species. Our study aimed to explore the training of primary chicken monocytes. We hypothesized that primary chicken monocytes, similar to their mammalian counterparts, can be trained with ß-glucan resulting in increased responses of these cells to a secondary stimulus. Primary blood monocytes of white leghorn chickens were primary stimulated with ß-glucan microparticulates (M-ßG), lipopolysaccharide (LPS), recombinant chicken interleukin-4 (IL-4) or combinations of these components for 48 h. On day 6, the primary stimulated cells were secondary stimulated with LPS. Nitric oxide (NO) production levels were measured as an indicator of pro-inflammatory activity. In addition, the cells were analyzed by flow cytometry to characterize the population of trained cells and to investigate the expression of surface markers associated with activation. After the secondary LPS stimulation, surface expression of colony stimulating factor 1 receptor (CSF1R) and the activation markers CD40 and major histocompatibility complex class II (MHC-II) was higher on macrophages that were trained with a combination of M-ßG and IL-4 compared to unstimulated cells. This increased expression was paralleled by enhanced NO production. In conclusion, this study showed that trained innate immunity can be induced in primary chicken monocytes with ß-glucan, which is in line with previous experiments in mammalian species. Innate immune training may have the potential to improve health and vaccination strategies within the poultry sector.

Chicken lines divergently selected on feather pecking differ in immune characteristics.

It is crucial to identify whether relations between immune characteristics and damaging behaviors in production animals exist, as these behaviors reduce animal welfare and productivity. Feather pecking (FP) is a damaging behavior in chickens, which involves hens pecking and pulling at feathers of conspecifics. To further identify relationships between the immune system and FP we characterized high FP (HFP) and low FP (LFP) selection lines with regard to nitric oxide (NO) production by monocytes, specific antibody (SpAb) titers, natural (auto)antibody (N(A)Ab) titers and immune cell subsets. NO production by monocytes was measured as indicator for innate pro-inflammatory immune functioning, SpAb titers were measured as part of the adaptive immune system and N(A)Ab titers were measured as they play an essential role in both innate and adaptive immunity. Immune cell subsets were measured to identify whether differences in immune characteristics were reflected by differences in the relative abundance of immune cell subsets. Divergent selection on FP affected NO production by monocytes, SpAb and N(A)Ab titers, but did not affect immune cell subsets. The HFP line showed higher NO production by monocytes and higher IgG N(A)Ab titers compared to the LFP line. Furthermore the HFP line tended to have lower IgM NAAb titers, but higher IgM and IgG SpAb titers compared to the LFP line. Thus, divergent selection on FP affects the innate and adaptive immune system, where the HFP line seems to have a more responsive immune system compared to the LFP line. Although causation cannot be established in the present study, it is clear that relationships between the immune system and FP exist. Therefore, it is important to take these relationships into account when selecting on behavioral or immunological traits.