Specific Humoral Immunity versus Polyclonal B Cell Activation in Trypanosoma cruzi Infection of Susceptible and Resistant Mice

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 10–12 million people in Latin America. Patent parasitemia develops during acute disease. During this phase, polyclonal B cell activation has been reported to generate high levels of serum antibody with low parasite specificity, and delayed protective humoral immunity, which is necessary to prevent the host from succumbing to infection. In this manuscript, data show that relatively resistant mice have improved parasite-specific humoral immunity and decreased polyclonal B cell activation compared to susceptible mice. Parasite-specific humoral immunity was associated with differential expansion of B cell subsets and T cells in the spleen, as well as with increased Th1 and decreased Th2 cytokine production. These data suggest that host susceptibility/genetic biases impact the development of humoral responses to infection. Th2 cytokines are generally associated with improved antibody responses. In the context of T. cruzi infection of susceptible mice, Th2 cytokines were associated with increased total antibody production concomitant with delayed pathogen-specific humoral immunity. This study highlights the need to consider the effect of host biases when investigating humoral immunity to any pathogen that has reported polyclonal B cell activation during infection

Vaccination of mice with a combination of BCG and killed Leishmania promastigotes reduces acute Trypanosoma cruzi infection by promoting an IFN-gamma response.

The combination of BCG with killed Leishmania promastigotes, demonstrated to be efficient in the cure of patients suffering American cutaneous leishmaniasis and in the induction of a long-term immune response in healthy vaccinated volunteers, was tested in BALB/c mice infected with Trypanosoma cruzi, in comparison to BCG or Leishmania alone, and a vehicle (PBS) control. BCG-Leishmania vaccination, applied intra-peritoneally 10 and 3 days before T. cruzi trypomastigote inoculation, prolonged the survival, and reduced blood parasitaemia of infected animals. Proliferation studies indicated that splenocytes of mice vaccinated with BCG-Leishmania and harvested in the acute phase of T. cruzi infection displayed stimulation indices higher than cells from PBS-treated mice when stimulated with PHA mitogen, PPD, Leishmania or T. cruzi antigens. Injections of a monoclonal antibody able to neutralise IFN-gamma into BCG-Leishmania vaccinated mice increased parasitaemia to levels similar to those of control animals (treated with PBS) and reversed the beneficial effect of vaccination on the proliferative response to T. cruzi antigen. These results show that vaccination of mice with BCG plus killed Leishmania promastigotes delayed acute T. cruzi infection, stimulated a T-cell response to T. cruzi antigen and promoted IFN-gamma production.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

An Fc gamma RII-, Fc gamma RIII-specific monoclonal antibody (2.4G2) decreases acute Trypanosoma cruzi infection in mice.

In order to study the role of Fc gamma Rs in Trypanosoma cruzi infection in mice, the 2.4G2 monoclonal antibody (MAb), specific to the extracellular domains of Fc gamma RII and Fc gamma RIII, was injected intraperitoneally into mice. Flow cytometry studies of uninfected mice showed that 2.4G2 MAb bound to peritoneal and lymph node cells, respectively, on days 2 and 6 after injection. Repeating 2.4G2 injections every 3 to 4 days decreased the availability of Fc gamma Rs on peritoneal, lymph node, and spleen cells. Injections of 2.4G2 MAb into T. cruzi-infected mice, at days -1, 3, 7, 11, 16, 20, and 24 relative to infection, reduced mortality in comparison with that in infected animals injected with an unrelated MAb (50 versus 93.3% mortality; P < 0.01). Parasitemia in 2.4G2-treated mice was significantly (three times) lower than in control animals on days 21 and 24 postinfection (P < 0.05), before parasite-specific antibodies were detectable at significant levels. Immunoglobulin and T. cruzi-specific antibody levels were similar in all groups of mice. These results indicate that repeated injections of 2.4G2 MAb administered to acutely infected mice reduce the in vivo infection level, suggesting that Fc gamma Rs play a role in the early host invasion by T. cruzi parasites

Maternal Trypanosoma cruzi-specific antibodies and worsening of acute infection in mouse offspring.

The role of antibodies in the previously demonstrated harmful effect of Trypanosoma cruzi-infected mothers on progeny infection was studied by injecting either serum from chronically infected animals or purified T. cruzi-specific antibodies into uninfected mice during gestation and lactation periods. It was verified that injected antibodies were transferred to offspring. Pregnant or lactating animals exhibited lower circulating antibody levels than nonpregnant or pregnant but nonlactating mice, respectively, suggesting that such antibody transfer occurred in both fetuses and suckling offspring. When infected two months after birth, offspring of mice treated with chronic serum or purified antibodies displayed significantly higher parasitemia than offspring from mothers receiving control serum or immunoglobulins unrelated to T. cruzi. These results indicate that soluble factors contained in sera of infected mice, and particularly antibodies, when transferred from mothers to their young, are able to worsen T. cruzi acquired infection in the offspring.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Opsonization of Toxoplasma gondii tachyzoites with nonspecific immunoglobulins promotes their phagocytosis by macrophages and inhibits their proliferation in nonphagocytic cells in tissue culture.

We have recently shown that Toxoplasma gondii tachyzoites grown in in vitro culture can bind unspecific immunoglobulin (Ig) through their Fc moiety. We show now that Fc receptors are also present on T. gondii within the host animal, and that intraperitoneal parasites in immunocompetent mice are saturated with unspecific Ig. We have also investigated the effect of the parasite's Fc receptor on the interaction of tachyzoites with mammalian cells, using the Vero cell line as a model for nonphagocytic host cells and murine peritoneal macrophages in primary culture as a model for phagocytic cells. Coating of tachyzoites with parasite-unrelated Ig did not enhance their invasive capacity in either target cell type, but slightly decreased the parasite proliferation. Moreover, phagocytosis by macrophages was increased by approximately 50% when parasites were coated with unspecific Ig. These results indicate that the Fc receptor on T. gondii affects the balance between invasion and phagocytosis in a way that is detrimental to the parasites.Comparative StudyJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

A Bibliometric Study on E-Learning Software Engineering Education

Due to the substantial development of information and communications technology, the use of E-learning in higher education has become essential to boost teaching methods and enhance students' learning skills and competencies. E-learning in Software Engineering turns out to be increasingly interesting for scholars. In fact, researchers have worked to enhance modern Software Engineering education techniques to meet the required educational objectives. The aim of this article is to analyse the scientific production on E-learning Software Engineering education by conducting a bibliometric analysis of 10,603 publications, dating from 1954 to 2020 and available in the Scopus database. The results reveal some scientific production information, such as the temporal evolution of the publications, the most prolific authors, institutions and countries, as well as the languages used. Besides, the paper evaluates additional bibliometric parameters, including the authors' production, journal productivity, and scientific cooperation, among other bibliometric parameters. The subject of the current study has not been treated by any previous bibliometric studies. Our research is deeper and more specific; it covers a long period of 66 years and a large number of publications, thanks to the chosen search string containing the different spellings of the used terms. In addition, the literature is analysed using several tools such as Microsoft Excel, VOSviewer, and Python. The research findings can be used to identify the current state of E-learning Software Engineering Education, as well as to identify various research trends and the general direction of E-learning research.