Immunization with Brucella abortus S19Δper Conferred Protection in Water Buffaloes against Virulent Challenge with B. abortus Strain S544.

Vaccination of cattle and buffaloes with Brucella abortus strain 19 has been the mainstay for control of bovine brucellosis. However, vaccination with S19 suffers major drawbacks in terms of its safety and interference with serodiagnosis of clinical infection. Brucella abortus S19∆per, a perosamine synthetase wbkB gene deletion mutant, overcomes the drawbacks of the S19 vaccine strain. The present study aimed to evaluate the potential of Brucella abortus S19Δper vaccine candidate in the natural host, buffaloes. Safety of S19∆per, for animals use, was assessed in guinea pigs. Protective efficacy of vaccine was assessed in buffaloes by immunizing with normal dose (4 × 1010 colony forming units (CFU)/animal) and reduced dose (2 × 109 CFU/animal) of S19Δper and challenged with virulent strain of B. abortus S544 on 300 days post immunization. Bacterial persistency of S19∆per was assessed in buffalo calves after 42 days of inoculation. Different serological, biochemical and pathological studies were performed to evaluate the S19∆per vaccine. The S19Δper immunized animals showed significantly low levels of anti-lipopolysaccharides (LPS) antibodies. All the immunized animals were protected against challenge infection with B. abortus S544. Sera from the majority of S19Δper immunized buffalo calves showed moderate to weak agglutination to RBPT antigen and thereby, could apparently be differentiated from S19 vaccinated and clinically-infected animals. The S19Δper was more sensitive to buffalo serum complement mediated lysis than its parent strain, S19. Animals culled at 6-weeks-post vaccination showed no gross lesions in organs and there was comparatively lower burden of infection in the lymph nodes of S19Δper immunized animals. With attributes of higher safety, strong protective efficacy and potential of differentiating infected from vaccinated animals (DIVA), S19Δper would be a prospective alternate to conventional S19 vaccines for control of bovine brucellosis as proven in buffaloes.

In vitro And In vivo Immunomodulating Properties of Mesenchymal Stem Cells.

BACKGROUND: Mesenchymal Stem Cells (MSCs) are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into all cell types of mesodermal origin, such as adipocytes, osteocytes and chondrocytes. Mesenchymal Stem Cells (MSCs) are adult stem cells which can be isolated from human and animal sources. OBJECTIVE: Besides the differentiation potential of MSCs, these also regulate the immune response in numerous ailments. The present review expedites the immunomodulating prospective of MSCs. METHODS: Scrupulous search of the literature and patents available on MSCs and their role in the immunomodulation was carried out using Medline, PubMed, PubMed Central, Science Direct and other scientific databases. The retrieved information has been analyzed and compiled. RESULTS: MSCs have unique regulation of microenvironment in the host tissue by secreting cytokines and immune-receptors which results in immunomodulatory effects. MSCs can be used as an effective tool in the treatment of chronic diseases because of its property to secrete anti-inflammatory molecules, having multilineage potential and immunomodulation. CONCLUSION: The present review is focused on the use of MSCs due to their unique immunomodulatory characteristics. MSCs reach to the site of inflammation and interact with immune cells to bring immunosuppressive and anti-inflammatory effects. Along with these unique therapeutic properties, MSCs may be a useful therapeutic approach for various disorders.

Effect of dietary mannanoligosaccharide supplementation on nutrient digestibility, hindgut fermentation, immune response and antioxidant indices in dogs.

BACKGROUND: Use of prebiotics in companion animal nutrition is often considered advantageous over probiotics because of the ease of handling, ability to withstand processing and storage etc. While most of the studies on prebiotic use in dogs have been done with processed food as basal diet, the response in relation to homemade diet feeding is not very well explored. METHODS: The study was conducted to evaluate the effects of dietary mannanoligosaccharide (MOS) supplementation on nutrient digestibility, hindgut fermentation, immune response and antioxidant indices in dogs. Ten Spitz pups were divided into two groups: control (CON) with no supplementation, and experimental (MOS) wherein the basal diet was supplemented with MOS at 15 g/kg diet. All dogs were fed on a home-prepared diet for a period of 150 days. The study protocol included a digestion trial, periodic blood collection and analysis for lipid profile and erythrocytic antioxidants. Immune response of the animals was assessed towards the end of the feeding period. RESULTS: Results revealed no significant (P > 0.05) variations in palatability score, intake and apparent digestibility of nutrients between the groups. Faecal score, faeces voided, faecal pH, concentrations of ammonia, lactate and short-chain fatty acids were comparable (P > 0.05) between the two groups. Cell-mediated immune response, assessed as delayed-type of hypersensitivity response, was significantly higher (P < 0.05) in the MOS group. The percent of lymphocyte sub-populations CD4+ and ratio of CD4+:CD8+ were also significantly (P < 0.05) higher in MOS group. The serum IgG levels were similar (P > 0.05) in both the groups. Supplementation of MOS lowered (P < 0.05) serum total- and LDL- cholesterol levels, when compared with the control group. The erythrocytic antioxidant indices were similar (P > 0.05) between the two groups. CONCLUSIONS: The results indicated that supplementation of MOS at the rate of 15 g/kg in the diet of dog augmented the cell-mediated immune response and serum lipid profile without any influences on digestibility of nutrients, hindgut fermentation and antioxidants indices.

Protein-L-Isoaspartyl Methyltransferase (PIMT) Is Required for Survival of Salmonella Typhimurium at 42°C and Contributes to the Virulence in Poultry.

Poultry birds are asymptomatic reservoir of Salmonella Typhimurium (S. Typhimurium) but act as source of human infection for this bacterium. Inside the poultry, S. Typhimurium experiences several stresses, 42°C body temperature of birds is one of them. Proteins are highly susceptible to temperature mediated damage. Conversion of protein bound aspartate (Asp) residues to iso-aspartate (iso-Asp) is one of such modifications that occur at elevated temperature. Iso-Asp formation has been linked to protein inactivation and compromised cellular survival. Protein-L-isoaspartyl methyltransferase (PIMT) can repair iso-Asp back to Asp, thus enhances the cellular survival at elevated temperature. Here, we show that the pimt gene deletion strain of S. Typhimurium (Δpimt mutant strain) is hypersensitive to 42°C in vitro. The hypersusceptibility of Δpimt strain is partially reversed by plasmid based complementation (trans-complementation) of Δpimt strain. Following oral inoculation, Δpimt strain showed defective colonization in poultry caecum, and compromised dissemination to spleen and liver. Interestingly, we have observed three and half folds induction of the PIMT protein following exposure of S. Typhimurium to 42°C. Our data suggest a novel role of pimt gene in the survival of S. Typhimurium at elevated temperature and virulence.

Intermediate rough Brucella abortus S19Δper mutant is DIVA enable, safe to pregnant guinea pigs and confers protection to mice.

Brucella abortus S19 is a smooth strain used as live vaccine against bovine brucellosis. Smooth lipopolysaccharide (LPS) is responsible for its residual virulence and serological interference. Rough mutants defective of LPS are more attenuated but confers lower level of protection. We describe a modified B. abortus S19 strain, named as S19Δper, which exhibits intermediate rough phenotype with residual O-polysaccharide (OPS). Deletion of perosamine synthetase gene resulted in substantial attenuation of S19Δper mutant without affecting immunogenic properties. It mounted strong immune response in Swiss albino mice and conferred protection similar to S19 vaccine. Immunized mice produced higher levels of IFN-γ, IgG2a and thus has immune response inclined towards Th1 cell mediated immunity. Sera from immunized animals did not show agglutination reaction with RBPT antigen and thus could serve as DIVA (Differentiating Infected from Vaccinated Animals) vaccine. S19Δper mutant displayed more susceptibility to serum complement mediated killing and sensitivity to polymyxin B. Pregnant guinea pigs injected with S19Δper mutant completed full term of pregnancy and did not cause abortion, still birth or birth of weak offspring. S19Δper mutant with intermediate rough phenotype displayed remarkable resemblance to S19 vaccine strain with improved properties of safety, immunogenicity and DIVA capability for control of bovine brucellosis.