About this Research Topic

Background

Tuberculosis (TB), caused by Mycobacterium tuberculosis complex organisms, is an infectious disease that represents the leading cause of morbidity and mortality among humans throughout the world. The most common form of the disease is pulmonary TB, although the pathogen can infect different tissues, including bones, lymph nodes, meninges, among others. Nonetheless, the majority of the estimated 1.7 billion infected people carry the bacteria in a dormant state, contained by the immune response, establishing a latent infection. However, individuals with latent infection can progress to active disease, which is usually associated with the development of compromised host immunity and immunodeficiencies.

Lack of efficient and cost-effective diagnostic tools, therapeutics, and prevention strategies contributes to poor control of TB in endemic countries. This situation is further complicated by the fact that BCG, the only available vaccine and approved by the World Health Organization to prevent TB, is only partially effective in preventing TB. The current standard treatment regimen for TB consists of 6 to 9 months of continuous antibiotic administration (Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol for the two first months followed by Isoniazid and Rifampicin four to seven months in the continuation phase). The prolonged duration of therapy with multiple antibiotics that have side effects pose significant challenges in patient compliance. Thus, many patients abandon treatment after the initial improvement of symptoms. This factor, combined with an inappropriate drug prescription, contributes significantly to the re-emergence of disease and the selection of antibiotic-resistant bacteria. That has led, in recent years, to the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains in the population, which requires further prolonged and more complicated treatment regimen. Taken together, these facts demonstrate an urgent need for the development of new methods to combat TB. Although several new antibiotics have been developed, especially for the treatment of drug-resistant strains, they usually induce severe side effects, which many times restricts their use. Further, the co-existence of TB with other diseases, such as diabetes, HIV-infection, and malnutrition, requires a more complicated treatment approach.

As an intracellular pathogen, M. tuberculosis survives and multiplies in many host innate cells by resisting the antimicrobial response posed by those cells. The intricate interaction between the host and pathogen-derived factors contribute to the outcome of infection. In general, the establishment of a protective immune response, marked by a proinflammatory M1 macrophage polarization and associated activation of Th1 response is critical for the control of M. tuberculosis replication in the host. However, in many cases, the cascade of the inflammatory response, elicited during infection, is detrimental to the host and causes significant tissue damage to infected organs, such as the lungs. Therefore, the host biological processes that contribute to TB pathogenesis and related host inflammatory response can be targeted for therapeutic interventions, which are known as host-directed therapies (HDTs). These approaches usually aim at targeting and/or optimizing host immune responses to suppress excessive detrimental inflammation and/or activate host antibacterial response. The most significant advantage of HDTs is that, by targeting host molecules and processes, not the pathogen itself, there should be no selection of drug-resistant bacteria. Further, HDT can aid in reducing the duration of treatment with fewer side-effects than conventional antibiotics therapy. These features make HDTs as a promising strategy for effective management of TB.

This Research Topic, therefore, welcomes the submission of Research Articles and Reviews focused on HDTs for all forms of TB as well as TB with associated comorbidities. Those may include all aspects of in vitro and in vivo research as well as methodologies and hypotheses that underpin promising HDTs development for TB.

Keywords: Host-directed Therapies, Tubercolosis, Mycobacterium tuberculosis, Multidrug Resistance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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