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Chronic bronchitis is currently diagnosed by asking patients if they expectorate sputum on a regular basis. In this study, the concentration of mucin was higher in the induced sputum of patients with chronic bronchitis than in those who did not meet the case definition of the disorder.

The pathogenesis of mucoinfective lung disease in cystic fibrosis (CF) patients likely involves poor mucus clearance. A recent model of mucus clearance predicts that mucus flow depends on the relative mucin concentration of the mucus layer compared with that of the periciliary layer; however, mucin concentrations have been difficult to measure in CF secretions. Here, we have shown that the concentration of mucin in CF sputum is low when measured by immunologically based techniques, and mass spectrometric analyses of CF mucins revealed mucin cleavage at antibody recognition sites. Using physical size exclusion chromatography/differential refractometry (SEC/dRI) techniques, we determined that mucin concentrations in CF secretions were higher than those in normal secretions. Measurements of partial osmotic pressures revealed that the partial osmotic pressure of CF sputum and the retained mucus in excised CF lungs were substantially greater than the partial osmotic pressure of normal secretions. Our data reveal that mucin concentration cannot be accurately measured immunologically in proteolytically active CF secretions; mucins are hyperconcentrated in CF secretions; and CF secretion osmotic pressures predict mucus layer-dependent osmotic compression of the periciliary liquid layer in CF lungs. Consequently, mucin hypersecretion likely produces mucus stasis, which contributes to key infectious and inflammatory components of CF lung disease.

Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB. We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance. We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB. CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV1, and both were significantly correlated. Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection is difficult to control because the virus undergoes antigenic variation during infection and also modulates the protective host immune response. Although current vaccines do not provide full protection, they have provided insight into the mechanisms of protection. Live PRRSV vaccines induce partial protection before the appearance of neutralizing antibody, suggesting cell-mediated immunity or other mechanisms may be involved. Herein, we demonstrate recovery from infection is associated with development of cytotoxic T-lymphocytes (CTL) that can kill PRRSV-infected target cells. Initial experiments showed survival of PRRSV-infected monocyte derived macrophage (MDM) targets is reduced when overlaid with peripheral blood mononuclear cells (PBMC) from gilts that had recovered from PRRSV infection. Further studies with PBMC depleted of either CD4+ or CD8+ T-cells and positively selected subpopulations of CD4+ and CD8+ T-cells showed that both CD4+ and CD8+ T-cells were involved in killing. Examination of killing at different time points revealed killing was biphasic and mediated by CTL of different phenotypes. CD4+CD8+high were associated with killing target cells infected for 3-6 hours. CD4+CD8- CTL were associated with killing at 16-24 hours. Thus, all the anti-PRRSV CTL activity in pigs was attributed to two phenotypes of CD4+ cells which is different from the anti-viral CD4-CD8+ CTL phenotype found in most other animals. These findings will be useful for evaluating CTL responses induced by current and future vaccines, guiding to a novel direction for future vaccine development.

Airway mucin secretion studies have focused on goblet cell responses to exogenous agonists almost to the exclusion of baseline mucin secretion (BLMS). In human bronchial epithelial cell cultures (HBECCs), maximal agonist-stimulated secretion exceeds baseline by ~3-fold as measured over hour-long periods, but mucin stores are discharged completely and require 24 h for full restoration. Hence, over 24 h, total baseline exceeds agonist-induced secretion by several-fold. Studies with HBECCs and mouse tracheas showed that BLMS is highly sensitive to mechanical stresses. Harvesting three consecutive 1 h baseline luminal incubations with HBECCs yielded equal rates of BLMS; however, lengthening the middle period to 72 h decreased the respective rate significantly, suggesting a stimulation of BLMS by the gentle washes of HBECC luminal surfaces. BLMS declined exponentially after washing HBECCs (t1/2 = 2.75 h), to rates approaching zero. HBECCs exposed to low perfusion rates exhibited spike-like increases in BLMS when flow was jumped 5-fold: BLMS increased >4 fold, then decreased within 5 min to a stable plateau at 1.5-2-fold over control. Higher flow jumps induced proportionally higher BLMS increases. Inducing mucous hyperplasia in HBECCs increased mucin production, BLMS and agonist-induced secretion. Mouse tracheal BLMS was ~6-fold higher during perfusion, than when flow was stopped. Munc13-2 null mouse tracheas, with their defect of accumulated cellular mucins, exhibited similar BLMS as WT, contrary to predictions of lower values. Graded mucous metaplasia induced in WT and Munc13-2 null tracheas with IL-13, caused proportional increases in BLMS, suggesting that naïve Munc13-2 mouse BLMS is elevated by increased mucin stores. We conclude that BLMS is, [i] a major component of mucin secretion in the lung, [ii] sustained by the mechanical activity of a dynamic lung, [iii] proportional to levels of mucin stores, and [iv] regulated differentially from agonist-induced mucin secretion.

Phylogenic comparisons of the mononuclear phagocyte system (MPS) of humans and mice demonstrate phenotypic divergence of dendritic cell (DC) subsets that play similar roles in innate and adaptive immunity. Although differing in phenotype, DC can be classified into four groups according to ontogeny and function: conventional DC (cDC1 and cDC2), plasmacytoid DC (pDC), and monocyte derived DC (MoDC). DC of Artiodactyla (pigs and ruminants) can also be sub-classified using this system, allowing direct functional and phenotypic comparison of MoDC and other DC subsets trafficking in blood (bDC). Because of the high volume of blood collections required to study DC, cattle offer the best opportunity to further our understanding of bDC and MoDC function in an outbred large animal species. As reported here, phenotyping DC using a monoclonal antibody (mAb) to CD209 revealed CD209 is expressed on the major myeloid population of DC present in blood and MoDC, providing a phenotypic link between these two subsets. Additionally, the present study demonstrates that CD209 is also expressed on monocyte derived macrophages (MoΦ). Functional analysis revealed each of these populations can take up and process antigens (Ags), present them to CD4 and CD8 T cells, and elicit a T-cell recall response. Thus, bDC, MoDC, and MoΦ pulsed with pathogens or candidate vaccine antigens can be used to study factors that modulate DC-driven T-cell priming and differentiation ex vivo.

SPAG6, an axoneme central apparatus protein, is essential for function of ependymal cell cilia and sperm flagella. A significant number of Spag6-deficient mice die with hydrocephalus, and surviving males are sterile because of sperm motility defects. In further exploring the ciliary dysfunction in Spag6-null mice, we discovered that cilia beat frequency was significantly reduced in tracheal epithelial cells, and that the beat was not synchronized. There was also a significant reduction in cilia density in both brain ependymal and trachea epithelial cells, and cilia arrays were disorganized. The orientation of basal feet, which determines the direction of axoneme orientation, was apparently random in Spag6-deficient mice, and there were reduced numbers of basal feet, consistent with reduced cilia density. The polarized epithelial cell morphology and distribution of intracellular mucin, α-tubulin, and the planar cell polarity protein, Vangl2, were lost in Spag6-deficient tracheal epithelial cells. Polarized epithelial cell morphology and polarized distribution of α-tubulin in tracheal epithelial cells was observed in one-week old wild-type mice, but not in the Spag6-deficient mice of the same age. Thus, the cilia and polarity defects appear prior to 7 days post-partum. These findings suggest that SPAG6 not only regulates cilia/flagellar motility, but that in its absence, ciliogenesis, axoneme orientation, and tracheal epithelial cell polarity are altered.

Background Periodontitis is common in dogs. It is characterized by destruction of the supporting tissues of the teeth due to the host-immune response triggered by plaque. Magnoliae cortex and Zea mays L. extract showed anti-inflammatory and anti-microbial effects, respectively. This study aimed to evaluate improvement in periodontitis following the administration of Magnoliae cortex and Zea mays L. extract in dogs. Periodontitis was experimentally induced in 10 beagle dogs. Five dogs were administered 40 mg of Magnoliae cortex extract and 20 mg of Zea mays L. extract orally once per day for 2 months (MZ group), whereas the other group received empty gelatin capsules (control group). Periodontal clinical parameters, complete blood count, serum chemistry parameters, and tissue inflammatory cytokines and chemokine expression were assessed before and after combined oral extracts administration. Results The complete blood count and serum chemistry results of all dogs were within normal ranges. Gingival inflammation in MZ group was significantly better than that in the control group at 4 and 8 weeks post-medication (PM; p  < 0.05). The periodontal pocket depth and clinical attachment loss at 8 weeks PM in the MZ group were significantly lower than the baseline values ( p  < 0.05). The incidence of bleeding on probing in the MZ group was significantly lower than that in the control group at 4 weeks PM ( p  < 0.05). Throughout the medication period, the percentages of CD4 + and CD8 + T cells were higher and lower, respectively, in the MZ group. However, these differences were only significant at 8 weeks PM. The expression of the inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α and the chemokine IL-8 in the inflamed tissues was lower in the MZ group, and the two groups showed a significant difference in TNF-α expression. Conclusions Combined administration of Magnoliae cortex and Zea mays L. extract improved the clinical symptoms of periodontal disease in dogs. This beneficial effect may be partly due to the inhibitory effects of these extracts on the inflammatory response.

Bovine tuberculosis (BTB), caused by , is a chronic infectious disease of major veterinary and public health concern. It affects a broad range of domestic and wild animals, including water buffalo, and poses a risk to humans due to its zoonotic nature. The economic consequences of BTB, arising from production losses and trade restrictions, further underline its global importance. While cattle immune responses to BTB are well characterized, the immune mechanisms in buffalo remain poorly understood, despite their increasing role as livestock in endemic regions. Given that buffaloes and cattle, although closely related, display notable immunological differences, comparative studies are essential. This study aimed to investigate and compare antigen-specific cytokine responses in CD4 T lymphocytes from buffaloes and cattle exposed to or infected with . A multicolor flow cytometry assay was established to enable high-resolution analysis of cytokine-expressing CD4 T cells. Blood samples were obtained from 35 buffaloes (17 IGRA-positive from BTB outbreak farms and 18 IGRA-negative, including animals from both outbreak and Officially Tuberculosis-Free [OTF] herds) and 10 cattle (6 IGRA-positive from a BTB outbreak farm and 4 IGRA-negative from an OTF herd). Following six hours of in vitro stimulation with PPD-B or PBS, intracellular cytokine staining was performed. This approach allowed simultaneous quantification of single and polyfunctional CD4 T cell subsets producing IFN-γ, TNF-α, and IL-17A. Data were analyzed using factor analysis of mixed data (FAMD) to explore species- and infection-related immune response patterns. The multicolor flow cytometry approach successfully identified distinct cytokine-producing CD4⁺ T cell populations in both species. Overlapping immune profiles were observed between buffaloes and cattle; however, specific subsets-including IL-17A , IFN-γ IL-17A , and TNF-α IL-17A cells-contributed to interspecies differences. Importantly, the frequency of IFN-γ and TNF-α producing CD4 T cells correlated with IGRA test status, enabling discrimination between infected/exposed and non-infected animals. These results demonstrate the ability of cytokine expression patterns to reflect both infection status and host species. The findings indicate that buffaloes and cattle share broadly similar antigen-specific cytokine responses, although subtle differences in CD4⁺ T cell subsets exist. The study highlights the value of multicolor flow cytometry as a high-resolution tool for dissecting immune responses in veterinary immunology. These insights enhance understanding of buffalo immune mechanisms against BTB and may contribute to improved disease control strategies.