Search

Exaggerated host innate immune responses have been implicated in severe influenza pneumonia. We have previously demonstrated that excessive neutrophils recruited during influenza infection drive pulmonary pathology through induction of neutrophil extracellular traps (NETs) and release of extracellular histones. Chemokine receptors (CRs) are essential in the recruitment and activation of leukocytes. Although neutrophils have been implicated in influenza pathogenesis, little is known about their phenotypic changes, including expression of CRs occurring in the infected -lung microenvironment. Here, we examined CC and CXC CRs detection in circulating as well as lung-recruited neutrophils during influenza infection in mice using flow cytometry analyses. Our studies revealed that lung-recruited neutrophils displayed induction of CRs, including CCR1, CCR2, CCR3, CCR5, CXCR1, CXCR3, and CXCR4, all of which were marginally induced in circulating neutrophils. CXCR2 was the most predominant CR observed in both circulating and lung-infiltrated neutrophils after infection. The stimulation of these induced CRs modulated neutrophil phagocytic activity, ligand-specific neutrophil migration, bacterial killing, and NETs induction ex vivo. These findings indicate that neutrophils induce a novel CR repertoire in the infectious lung microenvironment, which alters their functionality during influenza pneumonia.

Two 89-d experiments (Exp 1 and Exp 2) evaluated the effects of feeding an immunomodulatory feed additive (NutraGen; NG) in calves following exposure to bovine viral diarrhea virus (BVDV) on d -3 and Mannheimia haemolytica (MH) infection on d 0. For each experiment, steers [body weight (BW) = 251 ± 38.2 kg)] were randomly allocated to 1 of 3 treatments. Treatments included a placebo (CON; Exp 1 n = 5; Exp 2 n = 5), a placebo fed from d -18 to d -3 followed by NG fed from d -3 to d 28 (CHLG; Exp 1 n = 5; Exp 2 n = 6), and NG fed from d -18 to d 28 (PREC; Exp 1 n = 6; Exp 2 n = 5). Data were analyzed using the GLIMMIX procedure of SAS Version 9.4 (SAS Institute, Cary, N.C.). Animal served as the experimental unit and time served as a repeated measure. Treatment, time, and the treatment × time interaction served as fixed effects. Block was included as a random effect. Multiple treatment × time interactions and time effects occurred for serum glucose, lactate, blood urea nitrogen, and non-esterified fatty acid concentrations (P ≤ 0.003) in both experiments. There was a general trend for serum glucose to decrease over time postchallenge, suggesting increased cellular utilization of glucose in response to the challenge. In Exp 1, treatment effects occurred for serum glucose (P ≤ 0.001) and serum lactate (P ≤ 0.01), where calves assigned to the CHLG treatment displayed the greatest concentrations of the metabolites. Blood urea nitrogen concentrations peaked at h 48 in Exp 1 and h 6 in Exp 2. There were no treatment effects or treatment × time interactions for serum cortisol, hair cortisol, or fecal corticosterone concentrations in either experiment (P ≥ 0.17). There were, however, multiple time effects for serum cortisol, hair cortisol, and fecal corticosterone concentrations in both experiments (P ≤ 0.02), indicating that the challenge directly impacted cortisol and corticosterone production. Serum cortisol steadily increased from h 96 to h 168 in both experiments. Trends in cortisol and corticosterone production were similar in both experiments; however, peak concentration times for these variables occurred later in Exp 2. These data suggest that feeding NG to calves may alter glucose availability and nutrient utilization in response to infection resulting from a bovine respiratory disease challenge. [ABSTRACT FROM AUTHOR]

Two 89-d experiments (Exp 1 and Exp 2) evaluated the effects of feeding an immunomodulatory feed additive (NutraGen; NG) in calves following exposure to bovine viral diarrhea virus (BVDV) on d -3 and Mannheimia haemolytica (MH) infection on d 0. For each experiment, steers [body weight (BW = 251 ± 38.2 kg were randomly allocated to 1 of 3 treatments. Treatments included a placebo (CON; Exp 1 n = 5; Exp 2 n = 5), a placebo fed from d -18 to d -3 followed by NG fed from d -3 to d 28 (CHLG; Exp 1 n = 5; Exp 2 n = 6), and NG fed from d -18 to d 28 (PREC; Exp 1 n = 6; Exp 2 n = 5). Data were analyzed using the GLIMMIX procedure of SAS Version 9.4 (SAS Institute, Cary, N.C.). Animal served as the experimental unit and time served as a repeated measure. Treatment, time, and the treatment × time interaction served as fixed effects. Block was included as a random effect. Cytokine data were tested for normality using the Shapiro-Wilk test, determined to be non-normal, and logarithm (base 10) transformed as a result prior to statistical analysis. Multiple time effects and treatment × time interactions occurred for serum MH, BVDV 1, and BVDV 2 antibody concentrations in both experiments (P ≤ 0.05). In Exp 1, there was a tendency for an overall treatment effect for calves assigned to the CON treatment to exhibit the greatest MH serum antibody concentrations (P = 0.06). While no differences were detected between treatment groups, BVDV 1 and BVDV 2 antibody concentrations peaked on the same day in both experiments, d 28 post-challenge. There were no treatment × time interactions, treatment effects, or time effects for serum TNF-α, IFN-γ, or IL-17A concentrations (P ≥ 0.13) in either experiment. In Exp 1, there was a treatment effect for serum IL-10 (P ≤ 0.0001), where calves assigned to the PREC treatment had increased serum IL-10 concentrations when compared with calves in the other treatment groups. In Exp 2, there was a tendency for a treatment effect for IL-10 concentrations, where calves assigned to the PREC treatment displayed decreased IL-10 concentrations when compared with calves in the other treatment groups (P = 0.07). These data suggest that feeding NG to calves prior to a stress experience may alter cellular responses. Overall, these experiments suggest that NG impacted antibody concentrations and cytokine expression during a bovine respiratory disease challenge. [ABSTRACT FROM AUTHOR]

Two experiments (EXP1 and EXP2) evaluated the effects of NutraGen (NG) on calf health following exposure to bovine viral diarrhea virus (BVDV) on d -3 and Mannheimia haemolytica (Mh) infection on d 0. For each EXP, steers (BW = 251 ± 38.2 kg) were randomly allocated to 1 of 3 treatments (TRT). Treatments included a placebo (CON; EXP1 n = 5; EXP2 n = 5), a placebo fed from d -18 to d -3 followed by NG fed from d -3 to d 28 (CHLG; EXP1 n = 5; EXP2 n = 6), and NG fed from d -18 to d 28 (PREC; EXP1 n = 6; EXP2 n = 5). There was no treatment by time interaction (TRT×TME) or TRT effect for rectal temperatures (RT) or clinical scores (CS) in EXP1 or CS in EXP2 (P = 0.26). There was a TRT×TME for respiration rates (RR) during the first 24 h following Mh infection (P = 0.04), and a tendency for a TRT effect from d -3 to d 14, and overall in EXP1 (P ≥ 0.10). There was a tendency for a TRT×TME for RT from d -3 to d 14 in EXP2 (P = 0.04). There was a TRT effect for RR from d -3 to d 14 and overall in EXP2 (P ≥ 0.05). There was a TRT×TME for leukocytes during the first 24 h following Mh infection in EXP1 (P = 0.03) and overall in both EXP (P ≥ 0.001). There was no TRT×TME or TRT effect for neutrophils (NEU), lymphocytes (LYM), or NEU:LYM in EXP1 (P = 0.19); however, there were multiple TRT×TME and TRT effects for NEU, LYM, and NEU:LYM in EXP2 (P ≥ 0.05). These experiments suggest that NG has the potential to alter clinical and cellular responses during a bovine respiratory disease challenge. [ABSTRACT FROM AUTHOR]