The antigenic variability of tumor cells leading to dynamic changes in cancer epitope landscape along with escape from immune surveillance by down-regulating tumor antigen expression/presentation and immune tolerance are major obstacles for the design of effective vaccines. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response as well as HIV-neutralizing antibodies. In this proof-of-concept study, we tested immunogenic properties and anti-tumor effects of the VELs bearing survivin-derived CTL epitope (GWEPDDNPI) variants in an aggressive metastatic mouse 4T1 breast tumor model. The constructed VELs had complexities of 10,500 and 8,000 individual members, generated as combinatorial M13 phage display and synthetic peptide libraries, respectively, with structural composition GWXPXDXPI, where X is any of 20 natural amino acids. Statistically significant tumor growth inhibition was observed in BALB/c mice immunized with the VELs in both prophylactic and therapeutic settings. Vaccinated mice developed epitope-specific spleen cell and CD8+ IFN-γ+ T-cell responses that recognize more than 50% of the panel of 87 mutated epitope variants, as demonstrated in T-cell proliferation assays and FACS analysis. These data indicate the feasibility of the application of this new class of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against cancer.

Probiotics are considered living microorganisms that help preserve the health of the host who uses them. Bacillus are a genus of Gram-positive bacteria used as probiotics for animal and human consumption. They are currently distributed in various commercial forms. Two of the species used as probiotics are B. licheniformis and B. subtilis. Macrophages are central cells in the immune response, being fundamental in the elimination of microbial pathogens, for which they use various mechanisms, including the formation of extracellular traps (METs). There have been very few studies carried out on the participation of macrophages in response to the interaction of probiotics of the genus Bacillus with the host. In this work, we used macrophages from the J774A mouse cell line.1, and we found that they are susceptible to infection by the two Bacillus species. However, both species were eliminated as the infection progressed. Using confocal microscopy, we identified the formation of METs from the first hours of infection, which were characterized by the presence of myeloperoxidase (MPO) and citrullinated histone (Hit3Cit). Quantitative data on extracellular DNA release were also obtained; release was observed starting in the first hour of infection. The induction of METs by B. licheniformis caused a significant decrease in the colony-forming units (CFU) of Staphylococcus aureus. The induction of METS by bacteria of the Bacillus genus is a mechanism that participates in controlling the probiotic and potentially pathogenic bacteria such as S. aureus. The induction of METs to control pathogens may be a novel mechanism that could explain the beneficial effects of probiotics of the genus Bacillus.

No abstract

Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

La toxina Pet (plasmid-encoded toxin) producida por Escherichia coli (EAEC) es uno de los autotransportadores más estudiados en la familia Enterobacteriaceae.Es responsable de cambios morfológicos enenterocitos durante la infección por EAEC. Recientemente, Pet fue encontrada en el genoma de una cepa de Proteus mirabilis RTX339 [P. mirabilis (Pet+)]. P. mirabilis causa infección en el tracto urinario (ITU) en pacientes que usan catéteres o que presentan anomalías estructurales o funcionales. En este estudio una ITU con P. mirabilis (Pet+) fue inducida en ratones hembras BALB/c. Los ratones infectados con P. mirabilis (Pet+) muestran una colonización bacteriana en vejiga y riñón desde el segundo hasta el día decimo de la infección. Los cambios morfológicos fueron evidenciados por histología. Se observaron múltiples células exfoliadas del epitelio de transición de la vejiga, así como alteraciones morfológicas en la corteza renal. Se confirmó la presencia de Pet en las células exfoliadas y en las del parénquima por microscopíaconfocal. Las alteraciones del citoesqueleto fueron observadas en los sitios donde se detectó Pet. La toxina Pet expresada por la cepa de P. mirabilis (Pet+) contribuye a la patogenicidad y afecta tejidos urinarios durante el curso de la infección.

No abstract

Objective:To ascertain in ammatory response through interleukin 1 presence and identify pathogenic microorganisms as possible immunological and microbiological markers in diagnosis and treatment non-surgical periodontal in patients with gingivitis and moderate chronic periodontitis in a sample of Mexican population. Material and methods: In the present prospective cohort study, 18 patients with signs of gingivitis and 17 patients with moderate chronic periodontitis were selected. Samples of subgingival bio lm and of crevicular gingival uid were collected. Interleukin 1 was RESUMEN Objetivo: Conocer la respuesta in amatoria a través de la presencia de interleucina 1 e identi car microorganismos patógenos como posibles marcadores inmunológicos y microbiológicos en el diagnóstico y tratamiento periodontal no quirúrgico en sujetos con gingivitis y periodontitis crónica moderada en población mexicana. Material y métodos: En este estudio prospectivo de cohortes, se seleccionaron 18 pacientes con signos clínicos de gingivitis y 17 pacientes con periodontitis crónica moderada, se recolectaron las muestras de biopelícula subgingival y de uido gingival crevicular. Non surgical periodontal treatment in patients with gingivitis and moderate periodontitis. Biochemical and microbiological response Tratamiento periodontal no quirúrgico en pacientes con gingivitis y periodontitis moderada. Respuesta bioquímica y microbiológicaAbbreviations: Units Base 10 logarithm = log Microliters = L Milliliters = mL Pictograms = pg Percentage = % Revolutions per minute = rpm Seconds = sec www.medigraphic.org.mx pp e151-e160 e152 Macín-Cabrera S et al. Non surgical periodontal treatment. Biochemical and microbiological response www.medigraphic.org.mx

Actinomycetoma is a chronic subcutaneous lesion caused by the pathogenic bacterium Nocardia (N.) brasiliensis. Yeast antigens of Candida (C.) albicans increase the interferon (IFN)-γ and TCD4+ cells levels that enhance the phagocytic killing of N. brasiliensis, able to survive inside phagocytes and to grow in clustered colonies that form grains. The aim of this work was to test the effect of a crude protein extract of C. albicans on the levels of IFN-γ producing TCD4+ cells and on the outcome of actinomycetoma lesion. Five BALB/c mice with N. brasiliensis infection at left hind footpad were treated four times every other day with C. albicans crude protein extract (CPE). Five uninfected mice treated with CPE or infected mice treated with sterile phosphate-saline buffer were included as positive and negative control groups, respectively. Footpad thickness was recorded in all groups. Once the treatments were finished, single cell suspensions from blood and spleen were prepared for assessing the amount (%) of IFN-γ producing TCD4+ cells by cytofluorometry; presence of TCD4+ and IFN-γ in footpad sections was detected by immunofluorescence and immunohistochemistry, respectively. By comparison with the negative control group, infected mice treated with CPE had lower footpad thickness, higher percentage of blood and spleen IFN-γ producing TCD4+ cells as well as in situ presence of IFN-γ and TCD4+ cells. These findings showed that CPE from C. albicans displayed an immunoadjuvant activity that enhanced the presence of IFN-γ pro-* Corresponding author.A. Palma-Ramos et al. 298ducing TCD4+ cells and IFN-γ for the resolution of N. brasiliensis actinomycetoma in mice.