Molecular Characterization of Virus-induced Autoantibody Responses

Here we present a comprehensive molecular mapping of virus-induced autoimmune B cell responses obtained by serological identification of antigens by recombinant expression cloning analysis. Immunoscreening of cDNA expression libraries of various organs (lung, liver, and spleen) using sera from mice infected with cytopathic (vaccinia virus [VV]) or noncytopathic (lymphocytic choriomeningitis virus [LCMV]) viruses revealed a broad specificity of the elicited autoantibody response. Interestingly, the majority of the identified autoantigens have been previously described as autoantigens in humans. We found that induction of virus-induced autoantibodies of the immunoglobulin G class largely depends on the CD40–CD40L-mediated interaction between T and B cells. Furthermore, antibody titers against a number of autoantigens were comparable to the concomitantly induced antiviral antibody response. Comparison of serum reactivity against a selected panel of autoantigens after infection with VV, LCMV, or vesicular stomatitis virus showed that the different virus infections triggered distinct autoantibody responses, suggesting that virus infections may leave specific “autoantibody fingerprints” in the infected host

Antibacterial and anti-virulence activity of manuka honey against genetically diverse Staphylococcus pseudintermedius strains

Staphylococcus pseudintermedius causes opportunistic infections in dogs. It also has significant zoonotic potential, with the emergence of multidrug-resistance leading to difficulty treating both animal and human infections. Manuka honey has previously been reported to inhibit many bacterial pathogens including methicillin resistant Staphylococcus aureus and is successfully utilised in both clinical and veterinary practice. Here we evaluated the ability of manuka honey to inhibit strains of S. pseudintermedius growth alone and in combination with antibiotics, and its capacity to modulate virulence within multiple S. pseudintermedius. All 18 of the genetically diverse S. pseudintermedius strains sequenced and tested were inhibited by ≤ 12% (w/v) medical grade manuka honey, although tolerance to five clinically relevant antibiotics was observed. The susceptibility of the isolates to four of these antibiotics was significantly increased (p ≤0.05) when combined with sub lethal concentrations of honey, although sensitivity to oxacillin was decreased. Virulence (DNase, protease and haemolysin) activity was also significantly reduced (p ≤ 0.05) in over half of isolates when cultured with sub lethal concentrations of honey (13, 9 and 10 isolates respectively). These findings highlight the potential for manuka honey to be utilised against S. pseudintermedius infections. Importance: Staphylococcus pseudintermedius is an important member of the skin microbial community in animals and can cause opportunistic infections in both pets and their owners. The high incidence of antimicrobial resistance in S. pseudintermedius highlights that this opportunistic zoonotic pathogen can cause infections which require prolonged and intensive treatment to resolve. Manuka honey has proven efficacy against many bacterial pathogens and is an accepted topical treatment for infections in both veterinary and clinical practice so is a particularly appropriate antimicrobial for use with zoonotic pathogens such as S. pseudintermedius. Here we demonstrate that manuka honey is not only highly potent against novel multi-drug resistant S. pseudintermedius isolates, but also acts synergistically with clinically relevant antibiotics. In addition, manuka honey modulates S. pseudintermedius virulence activity, even at subinhibitory concentrations. In a clinical setting these attributes may assist in controlling infection, allowing a more rapid resolution and reducing antibiotic use

Determining control parameters for dendritic cell-cytotoxic T lymphocyte interaction

This article is not available through ChesterRep.Dendritic cells (DC) are potent immunostimulatory cells facilitating antigen transport to lymphoid tissues and providing efficient stimulation of T cells. A series of experimental studies in mice demonstrated that cytotoxic T lymphocytes (CTL) can be efficiently induced by adoptive transfer of antigen-presenting DC. However, the success of DC-based immunotherapeutic treatment of human cancer, for example, is still limited because the details of the regulation and kinetics of the DC-CTL interaction are not yet completely understood. Using a combination of experimental mouse studies, mathematical modeling, and nonlinear parameter estimation, we analyzed the population dynamics of DC-induced CTL responses. The model integrates a predator-prey-type interaction of DC and CTL with the non-linear compartmental dynamics of T cells. We found that T cell receptor avidity, the half-life of DC, and the rate of CTL-mediated DC-elimination are the major control parameters for optimal DC-induced CTL responses. For induction of high avidity CTL, the number of adoptively transferred DC was of minor importance once a minimal threshold of approximately 200 cells per spleen had been reached. Taken together, our study indicates that the availability of high avidity T cells in the recipient in combination with the optimal application regimen is of prime importance for successful DC-based immunotherapy.This article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies