Claudia Nobrega

Bio: Claudia Nobrega is an academic researcher from RMIT University. The author has contributed to research in topics: Immune system & Antigen. The author has an hindex of 9, co-authored 12 publications receiving 391 citations. Previous affiliations of Claudia Nobrega include Instituto de Biologia Molecular e Celular & University of Porto.

IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to Mycobacterium avium infection and influences efficacy of antibiotic therapy.

Abstract: Increased production of IL-10 has been frequently associated with augmented susceptibility to infection. However, the correlation between IL-10 activity and susceptibility to mycobacterial infection is still uncertain. Although studies using transgenic mice overexpressing IL-10 consistently showed an increased susceptibility to mycobacterial infection, experimental approaches in which IL-10 activity was reduced or abrogated originated inconclusive data. We show here that this controversy might be due to the mouse strains used in the various experimental procedures. Our results show that BALB/c mice are more susceptible than C57BL/6 to Mycobacterium avium infection. This increased susceptibility of BALB/c mice is, to a great extent, due to distinct activity of IL-10 between the two mouse strains. In accordance, reduction of IL-10 activity through the administration of anti-IL-10R mAb, or the absence of IL-10 as studied in IL-10 knockout mice, clearly decreased the susceptibility of BALB/c mice to M. avium but had a less obvious effect in C57BL/6 mice. Moreover, abrogation of IL-10 activity in infected BALB/c mice increased the efficacy of antimycobacterial therapy, whereas for the C57BL/6 mice it produced no effect. These observations show that the activity of IL-10 in response to the same mycobacterial stimulus influences not only the susceptibility to infection but also the efficacy of antimycobacterial therapy. This should now be considered in the context of human response to mycobacterial infection, particularly as a possible strategy to improve treatment against infections by mycobacteria.

T Cells Home to the Thymus and Control Infection

Abstract: The thymus is a target of multiple pathogens. How the immune system responds to thymic infection is largely unknown. Despite being considered an immune-privileged organ, we detect a mycobacteria-specific T cell response in the thymus following dissemination of Mycobacterium avium or Mycobacterium tuberculosis. This response includes proinflammatory cytokine production by mycobacteria-specific CD4(+) and CD8(+) T cells, which stimulates infected cells and controls bacterial growth in the thymus. Importantly, the responding T cells are mature peripheral T cells that recirculate back to the thymus. The recruitment of these cells is associated with an increased expression of Th1 chemokines and an enrichment of CXCR3(+) mycobacteria-specific T cells in the thymus. Finally, we demonstrate it is the mature T cells that home to the thymus that most efficiently control mycobacterial infection. Although the presence of mature T cells in the thymus has been recognized for some time, to our knowledge, these data are the first to show that T cell recirculation from the periphery to the thymus is a mechanism that allows the immune system to respond to thymic infection. Maintaining a functional thymic environment is essential to maintain T cell differentiation and prevent the emergence of central tolerance to the invading pathogens.

Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen

Abstract: The ability of the thymus to generate a population of T cells that is, for the most part, self-restricted and self-tolerant depends to a great extent on the Ags encountered during differentiation. We recently showed that mycobacteria disseminate to the thymus, which raised the questions of how mycobacteria within the thymus influence T cell differentiation and whether such an effect impacts host–pathogen interactions. Athymic nude mice were reconstituted with thymic grafts from Mycobacterium avium -infected or control noninfected donors. T cells generated from thymi of infected donors seemed generally normal, because they retained the ability to reconstitute the periphery and to respond to unspecific stimuli in vitro as well as to antigenic stimulation with third-party Ags, such as OVA, upon in vivo immunization. However, these cells were unable to mount a protective immune response against a challenge with M. avium . The observation that thymic infection interferes with T cell differentiation, generating T cells that are tolerant to pathogen-specific Ags, is of relevance to understand the immune response during chronic persistent infections. In addition, it has potential implications for the repertoire of T cells generated in patients with a mycobacterial infection recovering from severe lymphopenia, such as patients coinfected with HIV and receiving antiretroviral therapy.

IL-10: The Master Regulator of Immunity to Infection

Abstract: IL-10 is an anti-inflammatory cytokine. During infection it inhibits the activity of Th1 cells, NK cells, and macrophages, all of which are required for optimal pathogen clearance but also contribute to tissue damage. In consequence, IL-10 can both impede pathogen clearance and ameliorate immunopathology. Many different types of cells can produce IL-10, with the major source of IL-10 varying in different tissues or during acute or chronic stages of the same infection. The priming of these various IL-10-producing populations during infections is not well understood and it is not clear whether the cellular source of IL-10 during infection dictates its cellular target and thus its outcome. In this article we review the biology of IL-10, its cellular sources, and its role in viral, bacterial, and protozoal infections.

Cell-Mediated Immune Responses in Tuberculosis

Abstract: Tuberculosis is primarily a disease of the lung, and dissemination of the disease depends on productive infection of this critical organ. Upon aerosol infection with Mycobacterium tuberculosis (Mtb), the acquired cellular immune response is slow to be induced and to be expressed within the lung. This slowness allows infection to become well established; thus, the acquired response is expressed in an inflammatory site that has been initiated and modulated by the bacterium. Mtb has a variety of surface molecules that interact with the innate response, and this interaction along with the autoregulation of the immune response by several mechanisms results in less-than-optimal control of bacterial growth. To improve current vaccine strategies, we must understand the factors that mediate induction, expression, and regulation of the immune response in the lung. We must also determine how to induce both known and novel immunoprotective responses without inducing immunopathologic consequences.

Interleukin‐10: new perspectives on an old cytokine

Abstract: Interleukin-10 (IL-10) has long been recognized to have potent and broad-spectrum anti-inflammatory activity, which has been unequivocally established in various models of infection, inflammation, and even in cancer. However, because of the marginal successes of the initial clinical trials using recombinant IL-10, some of the interest in this cytokine as an anti-inflammatory therapeutic has diminished. New work showing IL-10 production from regulatory T cells and even T-helper 1 T cells has reinvigorated the field and revealed the power of this cytokine to influence immune responses. Furthermore, new preclinical studies suggest that combination therapies, using antibodies to IL-10 along with chemotherapy, can be effective in treating bacterial, viral, or neoplastic diseases. Studies to understand IL-10 gene expression in the various cell types may lead to new therapeutics to enhance or inhibit IL-10 production. In this review, we summarize what is known about the regulation of IL-10 gene expression by various immune cells. We speculate on the promise that this cytokine holds to influence immune responses and mitigate immune pathologies.

Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease

Abstract: Interleukin 10 (IL-10) is a cytokine with potent anti-inflammatory properties that plays a central role in limiting host immune response to pathogens, thereby preventing damage to the host and maintaining normal tissue homeostasis Dysregulation of IL-10 is associated with enhanced immunopathology in response to infection as well as increased risk for development of many autoimmune diseases Thus a fundamental understanding of IL-10 gene expression is critical for our comprehension of disease progression and resolution of host inflammatory response In this review, we discuss modes of regulation of IL-10 gene expression in immune effector cell types, including signal transduction, epigenetics, promoter architecture, and post-transcriptional regulation, and how aberrant regulation contributes to immunopathology and disease progression

Федеральное государственное бюджетное учреждение «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний» Сибирского отделения Российской академии медицинских наук, Кемерово, Россия

Abstract: Results. The incidence rate of significant non-cardiac occlusive stenotic lesions in patients with coronary artery disease (CAD), who had to undergo CABG, was 15,84 %. Simultaneous revascularization of coronary and non-coronary arteries was performed in 2,46 % of patients with CAD and PolyVD and multi-stage surgical proced ures were chosen in other cases. Conclusions. The outcomes of CAD surgical treatment were improved in this group of patients due to the implementation of a mul-