[This corrects the article on p. 217 in vol. 41.].

就“Mycobacterium”一词中文译名的商榷

Macrophage produced inducible nitric oxide synthase (iNOS) is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO) by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS), iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). To understand the synergistic effect of IFN-γ and TNF-α activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN-γ priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-γ and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-γ priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-α contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-γ stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced.

/pdf/investigating-the-role-of-tnf-a-and-ifn-g-activation-on-the-1wh89zappg.pdf

Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages

TNF signals through two distinct receptors, designated TNFR1 and TNFR2, which initiate diverse cellular effects that include cell survival, activation, differentiation, and proliferation and cell death. These cellular responses can promote immunological and inflammatory responses that eradicate infectious agents, but can also lead to local tissue injury at sites of infection and harmful systemic effects. Defining the molecular mechanisms involved in TNF responses, the effects of natural and experimental genetic diversity in TNF signalling and the effects of therapeutic blockade of TNF has increased our understanding of the key role that TNF plays in infectious disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/path.4187

Tumour necrosis factor in infectious disease.

NAD+ Depletion Triggers Macrophage Necroptosis, a Cell Death Pathway Exploited by Mycobacterium tuberculosis

// Eun Jeong Won 1,* , Jae Kyun Ju 2,* , Young-Nan Cho 3,* , Hye-Mi Jin 3 , Ki-Jeong Park 3 , Tae-Jong Kim 3 , Yong-Soo Kwon 4 , Hae Jin Kee 5 , Jung-Chul Kim 2 , Seung-Jung Kee 1 and Yong-Wook Park 3 1 Department of Laboratory Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 2 Department of Surgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 3 Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 4 Department of Pulmonary and Critical Care Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea 5 Heart Research Center, Chonnam National University Hospital, Gwangju, Republic of Korea * These authors have contributed equally to this work Correspondence to: Yong-Wook Park, email: // Seung-Jung Kee, email: // Keywords : cytotoxicity, chemokine, migration, mucosal-associated invariant T cells, mucosal-associated cancer Received : March 23, 2016 Accepted : July 27, 2016 Published : August 10, 2016 Abstract Mucosal-associated invariant T (MAIT) cells are an antimicrobial MR1-restricted T cell subset and play an important role in immune defense response to bacteria. However, little is known about the role of MAIT cells in cancer. The aims of this study were to examine the level and function of MAIT cells in cancer patients and to evaluate the clinical relevance of MAIT cell levels. Ninety-nine patients with cancer and 20 healthy controls were included in this study. Circulating MAIT cell levels were significantly reduced in patients with mucosal-associated cancers (MACs), such as gastric, colon and lung cancers, but their capacities for IFN-γ, IL-17, or TNF-α production were preserved. This MAIT cell deficiency was significantly correlated with N staging and carcinoembryonic antigen level. Percentages of MAIT cells were significantly higher in cancer tissue than in peripheral blood and immunofluorescent labeling showed MAIT cell infiltration into colon cancer tissues. Circulating MAIT cells exhibited high levels of CCR6 and CXCR6, and their corresponding chemokines, such as CCL20 and CXCL16, were strongly expressed in colon cancer tissues. Activated MAIT cells not only had lymphokine-activated killer activity, but they also had direct cytotoxicity on K562 cells via degranulation of granzyme B and perforin. This study primarily demonstrates that circulating MAIT cells are reduced in MAC patients due to migration to mucosal cancer tissues and they have the potential to kill cancer cells. In addition, this circulating MAIT cell deficiency is related to the degree of cancer progression in mucosal tissues.

/pdf/clinical-relevance-of-circulating-mucosal-associated-4l4etwqbh3.pdf

Clinical relevance of circulating mucosal-associated invariant T cell levels and their anti-cancer activity in patients with mucosal-associated cancer

Host immune response against Mycobacterium tuberculosis is mediated by cellular immunity, in which cytokines and Th1 cells play a critical role. In the process of control of the infection by mycobacteria, TNF-alpha seems to have a primordial function. This cytokine acts in synergy with IFN-gamma, stimulating the production of reactive nitrogen intermediates (RNIs), thus mediating the tuberculostatic function of macrophages, and also stimulating the migration of immune cells to the infection site, contributing to granuloma formation, which controls the disease progression. IFN-gamma is the main cytokine involved in the immune response against mycobacteria, and its major function is the activation of macrophages, allowing them to exert its microbicidal role functions. Different from TNF-alpha and IFN-gamma, IL-10 is considered primarily an inhibitory cytokine, important to an adequate balance between inflammatory and immunopathologic responses. The increase in IL-10 levels seems to support the survival of mycobacteria in the host. Although there is not yet conclusive studies concerning a clear dichotomy between Th1 and Th2 responses, involving protective immunity and susceptibility to the disease, respectively, we can suggest that the knowledge about this responses based on the prevailing cytokine profile can help to elucidate the immune response related to the protection against M. tuberculosis.

/pdf/role-of-tnf-alpha-ifn-gamma-and-il-10-in-the-development-of-1rzvqw7cmk.pdf

Role of TNF-Alpha, IFN-Gamma, and IL-10 in the Development of Pulmonary Tuberculosis.

Este estudo foi apoiado pelo Conselho Nacional de Pesquisa (CNPq) e pela Fundacao de Amparo a Pesquisa do Estado de Pernambuco (FACEPE).

Antigenic fractions of Leishmania (Viannia) braziliensis: the immune response characterization of patients at the initial phase of disease

American cutaneous leishmaniasis (ACL) has different clinical manifestations and those are dependent on the immunological status of the host. Since CD4+ and CD8+ T cells and its mediators play a fundamental role in the host response to Leishmania and that there is also a search for antigenic molecules to be used as future vaccines and tools for prognostic tests, this study characterized ACL patients immune response after stimulation with soluble and insoluble fractions of L. (V.) braziliensis. We demonstrated a prevailing production of the Th2 cytokines, IL-4 and IL-10, and a specific production of IFN-γ and TNF-α in patients before treatment. There was also a predominance of CD4+ T cells and a small percentage CD8+ T cells. The insoluble antigenic fraction primarily stimulated CD4+ T cells while the soluble antigenic fraction showed a mixed profile, with CD4+ T cells being the main responsible for Th2 cytokines and CD8+ T cells for Th1 cytokines. Therefore, our results showed that a down modulation of the Th1 type of response occurs in the initial phase of L. braziliensis disease being the antigenic fractions capable of stimulating a specific immune response.

© 2011 Blackwell Publishing Ltd

Maria Carolina Accioly Brelaz

Papers

Role of TNF-Alpha, IFN-Gamma, and IL-10 in the Development of Pulmonary Tuberculosis.

Antigenic fractions of Leishmania (Viannia) braziliensis: the immune response characterization of patients at the initial phase of disease

Leishmania (Viannia) braziliensis antigenic fractions: the immune response characterization of patients at the initial phase of disease