Advances in Immunotherapeutic Approaches to Tuberculosis

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About this Research Topic

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Background

Active tuberculosis (TB) remains a devastating infectious disease accounting for about 10 million morbidity and over 1 million annual mortality worldwide. Following aerosol transmission, most individuals develop latent infection without clinical symptoms, but 5-10% reactivate, manifesting active, mostly pulmonary disease. Protection, leading to latency, is mediated predominantly by T-helper 1 (Th1) cell immunity, but include also polyfunctional Th1 and Th17 cells, macrophages, neutrophils and NK cells. Recently, antibodies have been investigated for their possible protective role for passive and active protection (i.e. in latent infection). On the other hand, Th-2 cell-derived IL-4 cytokines and B cells may play a regulatory role in active disease. Besides screening for elevated TB-specific antibody levels may serve for early detection of infectious cases and hence help to reduce the transmission of the infection.

Mycobacteria survive within the adverse host environment by sensing and responding to a wide variety of microenvironments, including intracellular living in naïve and activated macrophages and evolving conditions within different types of granulomas. This complex background makes the identification of host protective molecular constituents of TB bacilli and of the cellular and humoral mediator of protection challenging and in need of continuing innovative research. The current research approaches involve genomic, transcriptomic, proteomic and metabolomic analysis of pulmonary and systemic immune reactions. These new techniques can discover new molecular targets from the host or the pathogen that can be used for the design of new forms of chemotherapy, targets for vaccine development or novel immunotherapeutic agents.

The long duration of established chemotherapy leads to defaults with detrimental impact; therefore, combining it with immunotherapy to shorten treatment regiments would benefit patients’ health and reduce transmission. This approach would benefit from study of mechanisms, which sustain the latency of infection (LTBI) in most naturally infected subjects and in the highly exposed but uninfected resisters (HEBUI). Special attention will be given to HIV-infection associated and to multidrug-resistant TB disease.

In this Research Topic, we aim to provide a comprehensive overview of and recent progress in the basic mechanisms governing host-pathogen interaction during TB infections. We welcome the submission of Original Research, Reviews, and Perspective articles covering, but not limited to, the following sub-topics:

1) Novel methodologies deciphering immune responses against TB.
2) Immune responses in humans with active TB, LTBI and/or HEBUI.
3) Novel approaches in the design of new immune interventions, including immunotherapy and new vaccines against TB.

We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.

Keywords: Society affiliation RT

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