Molecular mimicry of brucella melitensis epitopes in mouse and human arthritis

Brucellosis is one of the most frequent zoonosis worldwide. Infection is transferable to humans, where brucellosis is associated with high incidence of osteoarticular disease including osteomyelitis, arthritis and spondyloarthritis. Peripheral arthritis and sacroiliitis often develop in patients with no or low count of live Brucella. Recently, we demonstrated that mice develop spontaneous arthritis several weeks after acute infection when bacteria are already eradicated. We aim to decipher immune mechanism of the brucellosis-associated delayed arthritis that has not been elucidated so far

Protective effect of peptide vaccination in murine infection with influenza virus

Vaccination is a major tool to protect people from seasonal infections of different strains of influenza virus that presently infects millions of individuals worldwide. Virus genome is highly polymorphic, and universal vaccine that protects against permanently changing virus is still under development. Despite notable differences between humans and rodents in the disease course, immunobiology and clinical evaluations, murine infectious models remain one of the major tools to test approaches for influenza vaccine development

Brucella and Osteoarticular Cell Activation: Partners in Crime

Osteoarticular brucellosis is the most common presentation of human active disease although its prevalence varies widely. The three most common forms of osteoarticular involvement are sacroiliitis, spondylitis, and peripheral arthritis. The molecular mechanisms implicated in bone damage have been recently elucidated. B. abortus induces bone damage through diverse mechanisms in which TNF-α and the receptor activator of nuclear factor kappa-B ligand (RANKL)-the natural modulator of bone homeostasis are involved. These processes are driven by inflammatory cells, like monocytes/macrophages, neutrophils, Th17 CD4+ T, and B cells. In addition, Brucella abortus has a direct effect on osteoarticular cells and tilts homeostatic bone remodeling. These bacteria inhibit bone matrix deposition by osteoblasts (the only bone cells involved in bone deposition), and modify the phenotype of these cells to produce matrix metalloproteinases (MMPs) and cytokine secretion, contributing to bone matrix degradation. B. abortus also affects osteoclasts (cells naturally involved in bone resorption) by inducing an increase in osteoclastogenesis and osteoclast activation; thus, increasing mineral and organic bone matrix resorption, contributing to bone damage. Given that the pathology induced by Brucella species involved joint tissue, experiments conducted on synoviocytes revealed that besides inducing the activation of these cells to secrete chemokines, proinflammatory cytokines and MMPS, the infection also inhibits synoviocyte apoptosis. Brucella is an intracellular bacterium that replicates preferentially in the endoplasmic reticulum of macrophages. The analysis of B. abortus-infected synoviocytes indicated that bacteria also replicate in their reticulum suggesting that they could use this cell type for intracellular replication during the osteoarticular localization of the disease. Finally, the molecular mechanisms of osteoarticular brucellosis discovered recently shed light on how the interaction between B. abortus and immune and osteoarticular cells may play an important role in producing damage in joint and bone.Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Arriola Benitez, Paula Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

New arthritic pannus-specific protein promotes fibroblast motility and polarization

Rheumatoid arthritis (RA) is chronic inflammatory disease characterized by the development of hypercellular pannus tissue in the affected joints of patients. Pannus invasiveness and activation correlates with stronger tissue destruction and worse clinical prognosis. Using murine arthritis model, we recently discovered that synovial concentration of Collagen Triple Helix Repeat-containing 1 (CTHRC1) message and protein is directly correlated with arthritis severity. In carcinogenesis, overexpression of CTHRC1 is associated with enhanced metastatic potential of solid tumors and increased cell motility. Our goal is to investigate the mechanism of synovial cell motility and invasiveness and the role of non-canonical WNT signaling in pannus development

New serum biomarker for rheumatoid arthritis

Development of hypercellular invasive pannus tissue within synovial joints is a hallmark of Rheumatoid Arthritis (RA). Pannus produces proteases that damage bone and cartilage. Non-invasive monitoring of pannus activity is important for clinical assessment of patients as well as for control of the efficacy of therapeutic interventions. Available biomarkers are not satisfactory in terms of pannus specificity and sensitivity for monitoring local inflammation and bone erosion. Our goal is collecting clinical samples of synovial fluid and plasma from patients with RA and/or osteoarthritis (OA) to study the role of WNT signaling in pannus formation and developing set of serum biomarkers to monitor pannus activity

Molecular mimicry of brucella melitensis epitopes in mouse and human arthritis

Brucellosis is one of the most frequent zoonosis worldwide. Infection is transferable to humans, where brucellosis is associated with high incidence of osteoarticular disease including osteomyelitis, arthritis and spondyloarthritis. Peripheral arthritis and sacroiliitis often develop in patients with no or low count of live Brucella. Recently, we demonstrated that mice develop spontaneous arthritis several weeks after acute infection when bacteria are already eradicated. We aim to decipher immune mechanism of the brucellosis-associated delayed arthritis that has not been elucidated so far

Protective effect of peptide vaccination in murine infection with influenza virus

Vaccination is a major tool to protect people from seasonal infections of different strains of influenza virus that presently infects millions of individuals worldwide. Virus genome is highly polymorphic, and universal vaccine that protects against permanently changing virus is still under development. Despite notable differences between humans and rodents in the disease course, immunobiology and clinical evaluations, murine infectious models remain one of the major tools to test approaches for influenza vaccine development

Genetic homongeneity and major histocompatibility complex haplotyping of white mice

Inbred murine strains are generated to insure genetic homogeneity and uniqueness and define immune characteristics, like major histocompatibility complex (MHC) haplotype, of the experimental model. Maintaining of the perfect inbred stock leads to increased level of homozygosity and sometimes encounters a problem of inbreeding depression and consequently deviation from strict inbreeding protocol. Our goals are (i) study genetic homogeneity of mice in the colony, and (ii) haplotyping of H-2 complex (MHC in mice) in this strain