Camelid pathology submissions to veterinary diagnostic laboratories are on the rise given the increasing popularity and population of llamas and alpacas especially in the western United States. When compared to other animals, the field of camelid neoplasia has a relative paucity of cases reported in the literature. The Colorado State University Veterinary Diagnostic Laboratories (CSU-VDL) has had a steady increase in the numbers of camelid pathology submissions allowing for a robust review of diagnoses of neoplasia in new world camelids. Here we present a retrospective analysis of camelid neoplastic and proliferative lesions diagnosed at the CSU-VDL from 1995 to 2020, followed by an extensive literature review. Results show increasing incidence of camelid neoplasia reported in the literature, therefore becoming a common diagnosis in llamas and alpacas. Proliferative and neoplastic lesions were diagnosed in 8.8% of new world camelid submissions to CSU-VDL with the most common tumors being lymphomas, squamous cell carcinomas, fibromas, and adenocarcinomas. Risk factors are female sex and increased age except in the case of lymphoma, which tends to occur in younger camelids. Lymphomas, melanomas, and adenocarcinomas (especially of gastrointestinal tract) carry an increased risk of multiple-organ system involvement often with widespread metastases. Conditions described in camelids for the first time include osteosarcoma, cutaneous hemangiosarcoma, myxosarcoma, pilomatricoma, ovarian theca cell tumor, congenital nevus with malignant transformation, and various other neoplasia. This article will provide an operational guide for camelid neoplasia to further assist veterinary laboratory diagnosticians, researchers, and practicing veterinarians in the field of camelid medicine and pathology.
Lactic acid bacteria (LAB) are Gram-positive, acid-tolerant bacteria that have long been used in food fermentation and are generally recognized as safe (GRAS). LAB are a part of a normal microbiome and act as probiotics, improving the gastrointestinal microbiome and health when consumed. An increasing body of research has shown the importance of the microbiome on both mucosal immune heath and immune response to pathogens and oral vaccines. Currently, there are few approved mucosal vaccines, and most are attenuated viruses or bacteria, which necessitates cold chain, carries the risk of reversion to virulence, and can have limited efficacy in individuals with poor mucosal health. On account of these limitations, new types of mucosal vaccine vectors are necessary. There has been increasing interest and success in developing recombinant LAB as next generation mucosal vaccine vectors due to their natural acid and bile resistance, stability at room temperature, endogenous activation of innate and adaptive immune responses, and the development of molecular techniques that allow for manipulation of their genomes. To enhance the immunogenicity of these LAB vaccines, numerous adjuvant strategies have been successfully employed. Here, we review these adjuvant strategies and their mechanisms of action which include: Toll-like receptor ligands, secretion of bacterial toxins, secretion of cytokines, direct delivery to antigen presenting cells, and enterocyte targeting. The ability to increase the immune response to LAB vaccines gives them the potential to be powerful mucosal vaccine vectors against mucosal pathogens.
Feline infectious peritonitis is a devastating, fatal disease of domestic cats caused by a pathogenic mutant virus derived from the ubiquitous feline enteric coronavirus (FECV). Infection by FECV is generally subclinical, and little is known about the mucosal immune response that controls and eliminates the virus. We investigated the mucosal immune response against FECV in an endemically infected breeding colony over a seven-month period. Thirty-three cats were grouped according to FECV seropositivity and fecal virus shedding into naïve/immunologically quiescent, convalescent and actively infected groups. Blood, fecal samples and colon biopsies were collected to assess the mucosal and systemic immunologic and virologic profile. Results showed that cats with active FECV infections have strong systemic IgG and mucosal IgA responses that wane after virus clearance. Significant FECV-specific mucosal T cell IFNγ responses were not detected in any of the three groups. A shift toward an inflammatory state in the mucosa was suggested by increased IL17:FoxP3 expression. However, no histologic abnormalities were observed, and no shifts in lymphocyte subpopulation phenotype or proliferation were noted. Together, the results suggest that control of FECV is mediated by humoral mucosal and systemic responses and that perturbations in the primary reservoir organ (colon) are minimal.
Unique to mucosal vaccination is the reciprocal influence of the microbiome and mucosal immune responses, where the immune system is constantly balancing between the clearance of pathogens and the tolerance of self-antigen, food, and the microbiota. Secretory IgA plays a major role in maintaining the homeostasis of a healthy gut microbiome. Natural polyreactive IgA often coats members of the commensal microbiota to aid in their colonization, while high-affinity specific IgA binds to pathogens resulting in their clearance. We developed a probiotic-based mucosal vaccination platform using the bacterium Lactobacillus acidophilus (rLA) with the potential to influence this balance in the IgA coating. In this study, we sought to determine whether repeated administration of rLA alters the host intestinal microbial community due to the immune response against the rLA vaccine. To address this, IgA-seq was employed to characterize shifts in IgA-bound bacterial populations. Additionally, we determined whether using rice bran as a prebiotic would influence the immunogenicity of the vaccine and/or IgA-bound bacterial populations. Our results show that the prebiotic influenced the kinetics of rLA antibody induction and that the rLA platform did not cause lasting disturbances to the microbiome.
Background Malnutrition and diarrhea are leading causes of death in children under five years old. Rice bran is a nutrient dense prebiotic available globally. Objectives The objective of this secondary analysis was to evaluate the effects of daily rice bran supplementation on environmental enteric dysfunction (EED) markers, total fecal secretory IgA (sIgA), and microbiota in infants at high-risk for malnutrition. Methods 6-month-old Malian and Nicaraguan infants were randomized to control or daily rice bran supplementation cohorts (1 to 5 grams/day). Feces were collected monthly for 6 months to evaluate fecal sIgA, markers of EED, and microbiota diversity. Statistical methods included linear mixed models, generalized mixed models, Spearman correlation, and Wilcoxon rank-sum tests. Results Six-month old Malian infants had significantly elevated sIgA (4.0X higher, P < 0.001), fecal myeloperoxidase (31.6X higher, P < 0.001), fecal alpha-1-antitrypsin (1.8X higher, P = 0.006), and lower fecal neopterin (0.13X higher, P < 0.001) than the age-matched Nicaraguan infants. In the Nicaraguan rice bran cohort from 6 to 12-months of age, there was a significant decrease in sIgA concentrations (0.4X, P < 0.05) and a correlation between sIgA and the EED marker alpha-1 antitrypsin (0.523, P < 0.0001) at 12 months of age. In Malian infants, daily rice bran ingestion resulted in decreased EED scores (0.71X, P = 0.02) and a stable sIgA concentration over time. The rice bran group of Mali infants also had correlation between sIgA and the EED marker neopterin (0.544, P < 0.001) at 12 months of age and a significant (P < 0.05) increase in microbiota ɑ-diversity at a younger age (9 months with rice bran versus 10 months of age in control group), which supports earlier microbiota maturation. Conclusion These results support rice bran as a functional food ingredient targeting gut mucosa in children at high-risk for malnutrition.
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