Predicting the Role of IL-10 in the Regulation of the Adaptive Immune Responses in Mycobacterium avium Subsp. paratuberculosis Infections Using Mathematical Models

Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular bacterial pathogen that causes Johne’s disease (JD) in cattle and other animals. The hallmark of MAP infection in the early stages is a strong protective cell-mediated immune response (Th1-type), characterized by antigen-specific γ-interferon (IFN-γ). The Th1 response wanes with disease progression and is supplanted by a non-protective humoral immune response (Th2-type). Interleukin-10 (IL-10) is believed to play a critical role in the regulation of host immune responses to MAP infection and potentially orchestrate the reversal of Th1/Th2 immune dominance during disease progression. However, how its role correlates with MAP infection remains to be completely deciphered. We developed mathematical models to explain probable mechanisms for IL-10 involvement in MAP infection. We tested our models with IL-4, IL-10, IFN-γ, and MAP fecal shedding data collected from calves that were experimentally infected and followed over a period of 360 days in the study of Stabel and Robbe-Austerman (2011). Our models predicted that IL-10 can have different roles during MAP infection, (i) it can suppress the Th1 expression, (ii) can enhance Th2 (IL-4) expression, and (iii) can suppress the Th1 expression in synergy with IL-4. In these predicted roles, suppression of Th1 responses was correlated with increased number of MAP. We also predicted that Th1-mediated responses (IFN-γ) can lead to high expression of IL-10 and that infection burden regulates Th2 suppression by the Th1 response. Our models highlight areas where more experimental data is required to refine our model assumptions, and further test and investigate the role of IL-10 in MAP infection

Do Profitable Farms Remain Profitable? Transition Probabilities Using Markov Switching Models Applied to Kansas Farm Data

Financial vulnerability has been observed across agricultural production regions; however, uncertainty regarding farms’ persistence within specific profitability categories exists. This study compared farm characteristics that persist in most and least profitable categories and then evaluated the probability that farms transitioned among profitability categories. Using 425 Kansas Farm Management Association (KFMA) farms that were present for the 20-year period 1994–2013, the persistence of remaining or transitioning to another profitability category was tested. Specifically, Markov transition probabilities were estimated for Kansas and the six regional KFMA regions. Comparisons of farms that persist in the highest and lowest profitability categories revealed no dramatic differences in acreage or other physical characteristics. Kansas farms tend to persist in their current profitability category, suggesting that operator skill and/or quality of farmland dominate random factors. In general, transition probabilities were greater for the highest and lowest profitability categories than for the middle categories. Farms were observed switching from highest to lowest profitability categories between 5% and 20% of the time within one year. Farmers were likely to stay in the highest profitability group more than half the time. By contrast, farmers were likely to stay in the lowest profitability group 42% of the time. Just like with the most profitable group, the least profitable group has a greater likelihood of remaining at the bottom, indicating that random events do not cause persistence

Quantitative Effect of Porcine Reproductive Respiratory Syndrome Virus on Pig Growth and Immune Response

Forty-eight pigs from a herd naïve for porcine reproductive respiratory syndrome virus (PRRS) were weaned, placed in isolation chambers, and oral-nasally inoculated with 2 ml of 10 4 JA142 PRRS virus. For each pig, body weight, feed intake, and serum concentration of PRRS virus titers, gamma-interferon (γ-IFN), and alpha-1- glycoprotein (AGP) were determined every 4 days for 24 days post-inoculation to determine the effect of PRRS exposure on growth and immune response in pigs and to quantify the relationship between serum virus concentration and pig growth. Serum virus titers and γ-IFN, both peaked at 4 days post-inoculation, and then declined steadily throughout the 24 day study. As expected, serum AGP responses were delayed with peak concentrations occurring 12 days post-inoculation. Body weight gains and feed intakes of individual pigs were quantitatively related to the animal’s serum concentration of virus titers and to a lessor degree to serum concentration of γ-IFN and AGP. Specifically, each additional 10-fold of serum virus titer was associated with a mean reduction of .018 kg in daily pig gain and .028 kg in daily pig feed consumption. These data indicate that the magnitude of biological responses that occur in pigs infected with PRRS is directly related to the animal’s serum virus concentration

Prevention of Mycobacterium avium Subspecies paratuberculosis (MAP) Infection in Balb/c mice by Feeding Lactobacillus acidophilus Strain NP-51®

The immune responses of 390 BALB/c mice fed the probiotic Lactobacillus acidophilus strain NP51 ® and infected with Mycobacterium avium subspecies paratuberculosis (MAP) were evaluated in a 6-month trial. Mice were randomized to nine treatment groups that fed either viable- or heat-killed NP51 and inoculated with either viable- or heatkilled MAP or sterile phosphate-buffered saline. Feeding the NP51 resulted in higher numbers of T lymphocytes in the spleen including the CD8 + cytotoxic T lymphocytes. In addition, feeding the NP51 lowered the number of immune suppressive T regulatory cells CD4 + CD25 + and CD8 + CD25 + cells in the spleen. Additionally, feeding the NP51 resulted in higher concentration of interferon-gamma in the supernatant of splenocytes cultured in vitro. These results suggest that feeding the NP51 to BALB/c mice might prevent the progression of MAP infection in mice

Early Epithelial Invasion by Salmonella enterica Serovar Typhimurium DT104 in the Swine Ileum

Salmonella enterica serovar Typhimurium is an important intestinal pathogen in swine. This study was performed to document the early cellular invasion of Salmonellaserovar Typhimurium in swine ileum. Ileal gut-loops were surgically prepared in ten 4- to 5-week-old mixed-breed pigs and inoculated for 0-60 minutes. Loops were harvested and prepared for both scanning and transmission electron microscopy (SEM and TEM, respectively). Preferential bacterial adherence to microfold cells (M cells) was seen within 5 minutes, and by 10 minutes bacterial invasion of the apical membrane was seen in M cells, goblet cells, and enterocytes. This multicellular invasion was observed throughout the course of infection. In addition, SEM revealed a specific affinity of Salmonella serovar Typhimurium to sites of cell extrusion. Using TEM, bacteria in these areas were focused in the crevices formed by the extruding cell and the adjacent cells and in the cytoplasm immediately beneath the extruding cell. Our results suggest that early cellular invasion by Salmonella serovar Typhimurium is nonspecific and rapid in swine. Furthermore, the combination of SEM and TEM data suggests that Salmonella serovar Typhimurium may use sites of cell extrusion as an additional mechanism for early invasion

Aestipascuomyces dupliciliberans gen. nov, sp. nov., the First Cultured Representative of the Uncultured SK4 Clade from Aoudad Sheep and Alpaca

We report on the isolation of the previously-uncultured Neocallimastigomycota SK4 lineage, by two independent research groups, from a wild aoudad sheep rumen sample (Texas, USA) and an alpaca fecal sample (Baden-Württemberg, Germany). Isolates from both locations showed near-identical morphological and microscopic features, forming medium-sized (2–5 mm) white filamentous colonies with a white center of sporangia, on agar roll tubes and a heavy biofilm in liquid media. Microscopic analysis revealed monocentric thalli, and spherical polyflagellated zoospores with 7–20 flagella. Zoospore release occurred through an apical pore as well as by sporangial wall rupturing, a duality that is unique amongst described anaerobic gut fungal strains. Isolates were capable of growing on a wide range of mono-, oligo-, and polysaccharide substrates as the sole carbon source. Phylogenetic assessment based on the D1–D2 28S large rRNA gene subunit (D1–D2 LSU) and internal transcribed spacer-1 (ITS-1) regions demonstrated high sequence identity (minimum identity of 99.07% and 96.96%, respectively) between all isolates; but low sequence identity (92.4% and 86.7%, respectively) to their closest cultured relatives. D1–D2 LSU phylogenetic trees grouped the isolates as a new monophyletic clade within the Orpinomyces–Neocallimastix–Pecoramyces–Feramyces–Ghazallamyces supragenus group. D1–D2 LSU and ITS-1 sequences recovered from the obtained isolates were either identical or displayed extremely high sequence similarity to sequences recovered from the same aoudad sheep sample on which isolation was conducted, as well as several sequences recovered from domestic sheep and few other herbivores. Interestingly, members of the SK4 clade seem to be encountered preferably in animals grazing on summer pasture. We hence propose accommodating these novel isolates in a new genus, Aestipascuomyces (derived from the Latin word for “summer pasture”), and a new species, A. dupliciliberans. The type strain is Aestipascuomycesdupliciliberans strain R4