Early-life ß-glucan exposure enhances disease resilience of broiler chickens to a natural Clostridium perfringens infection.

Necrotic enteritis (NE) is an economically important disease in poultry. Colonization by the opportunistic pathogen C. perfringens occurs early after hatch and induces host immune tolerance, which allows it to persist as part of the bird's commensal microflora. ß-glucan, a yeast cell wall component, is well characterized for its immunomodulatory capacity, and is a strong driver of innate immune memory. In this study, we assessed the effectiveness of ß-glucan to reduce severity of NE, when co-administered with heat-killed C. perfringens via intra-abdominal route at day 1 of age. We found that this early-life exposure in the presence of ß-glucan did not reduce intestinal C. perfringens loads or lesion severity during a subsequent NE outbreak. However, it improved ileal morphology, prevented liver and spleen weight decline, and preserved feed efficiency in challenged birds. Molecular analyses revealed metabolic changes consistent with innate immune memory. Together, our results suggest that ß-glucan can reduce the negative impacts of NE by influencing the context in which C. perfringens is first encountered.

A Poultry Subclinical Necrotic Enteritis Disease Model Based on Natural Clostridium perfringens Uptake.

Necrotic enteritis (NE) in poultry is an opportunistic infection caused by Clostridium perfringens. Well-known as a multifactorial disease, NE development is under the influence of a wide range of environmental risk factors that promote the proliferation of pathogenic C. perfringens at the expense of nonpathogenic strains. Current in vivo NE challenge models typically incorporate pre-exposure to disease risk factors, in combination with exogenous C. perfringens inoculation. Our goal was to enhance current models using a natural uptake of C. perfringens from the barn environment to produce a subclinical infection. We incorporated access to litter, coccidial exposure (either 10× or 15× of the manufacturer-recommended Coccivac B52 Eimeria vaccine challenge; provided unspecified doses of E. acervulina, E. mivati, E. tenella, and two strains of E. maxima), feed composition, and feed withdrawal stress, and achieved the commonly observed NE infection peak at 3 weeks post-hatch. NE severity was evaluated based on gut lesion pathology, clinical signs, and mortality rate. Under cage-reared conditions, 15× coccidial vaccine-challenged birds showed overall NE lesion prevalence that was 8-fold higher than 10× coccidial vaccine-challenged birds. NE-associated mortality was observed only in a floor-reared flock after a 15× coccidial vaccine challenge.

Impact of Reduced Dietary Crude Protein in the Starter Phase on Immune Development and Response of Broilers Throughout the Growth Period.

Crude protein (CP) levels in commercial broiler (Gallus gallus) diets, optimized for maximum yield production vs. feed cost, have only begun to be assessed for impact on immune function. In order to study immune effects of dietary CP levels, different starter phase (day 1-14) diets were fed to 230 Ross 708 male broiler chicks randomly assigned at 1 day of age into two treatment groups. Group 1: Standard diet (STD) contained 3,000 kcal AMEn/kg energy and 23.78% CP; and Group 2: Reduced crude protein diet (RCP) contained 3,000 kcal AMEn/kg energy and 21.23% CP. From day 15-35 a common standard grower/finisher diet (3,150 kcal AMEn/kg energy and 22.18% CP) was allocated to both groups. Zymosan, a glycan derived from yeast cell walls that binds to TLR 2 and Dectin-1, was used for intra-abdominal challenge. Results demonstrated that a reduced crude protein starter diet (21.23 vs. 23.78% CP) between age 1-14, while maintaining the same levels of metabolizable energy and essential amino acids, did not affect broilers growth performance or lymphoid organ weights (P > 0.05). Interestingly, basal leukocyte levels in the RCP group significantly (P < 0.01) increased in the blood compartment at d35 in the unchallenged birds. Significant enhancements to leukocyte infiltration into the abdominal cavity were also detected post-immune challenge with zymosan (day 14 and day 35; P < 0.01). Post-challenge levels of TNF-α, IL-1ß, and CXCL8 gene expression cells collected from the abdominal cavity were not affected by the diets (P > 0.05). Moreover, dietary treatments did not influence percentage of ROS producing cells in the abdominal cavity (P > 0.05). To our best knowledge, this is the first study that reports the impacts of reduced crude protein diet on the innate immune response of poultry to an acute inflammation model in the abdominal cavity. Overall, our results highlight that reduced crude protein diets can be used without negatively impacting broiler performance and may enhance the capacity of broilers to recruit leukocytes upon infection.

Bclaf1 critically regulates the type I interferon response and is degraded by alphaherpesvirus US3.

Type I interferon response plays a prominent role against viral infection, which is frequently disrupted by viruses. Here, we report Bcl-2 associated transcription factor 1 (Bclaf1) is degraded during the alphaherpesvirus Pseudorabies virus (PRV) and Herpes simplex virus type 1 (HSV-1) infections through the viral protein US3. We further reveal that Bclaf1 functions critically in type I interferon signaling. Knockdown or knockout of Bclaf1 in cells significantly impairs interferon-α (IFNα) -mediated gene transcription and viral inhibition against US3 deficient PRV and HSV-1. Mechanistically, Bclaf1 maintains a mechanism allowing STAT1 and STAT2 to be efficiently phosphorylated in response to IFNα, and more importantly, facilitates IFN-stimulated gene factor 3 (ISGF3) binding with IFN-stimulated response elements (ISRE) for efficient gene transcription by directly interacting with ISRE and STAT2. Our studies establish the importance of Bclaf1 in IFNα-induced antiviral immunity and in the control of viral infections.