Editorial: Beneficial and detrimental host cellular responses against Mycobacterium tuberculosis infection

Abstract

Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis (Mtb), an exceptionally successful pathogen. In fact, it is estimated that Mtb has killed nearly 1000 million people since the XIX century. The most updated mortality data indicate that in 2021, 1.4 million people died of TB (World Health Organization, 2022), converting this pathogenic bacteria into the second leading infectious cause of death globally after COVID-19. Mtb, a microorganism that has produced suffering and death since it was identified almost 150 years ago, urgently requires a better vaccine to prevent TB-dependent morbidity and mortality (Rahlwes et al., 2023). The immune response against Mtb is highly complex. Mtb invades humans by air and establishes infection in the lung by using a large number of different virulence factors. After infection, Mtb interacts with different cells of the innate and adaptive immune compartments. These cells play an important role in the modulation and development of the pathology. Mtb-infected alveolar macrophages and dendritic cells are both reservoirs of infection and function to activate an adaptive immune response. Mtb-infected cells migrate from the lung to draining lymph nodes to prime and activate T and B cells to limit progression of infection (Urdahl et al., 2011; Shaler et al., 2012; Carpenter and Lu, 2022). Infected macrophages, along with non-infected phagocytes, (macrophages, monocytes and neutrophils), and T cells recruited by the inflammation and tissue damage will in turn form the characteristic TB granuloma (Cohen et al., 2022; Cronan, 2022). A well-formed granuloma prevents the progression of infection, limiting tissue damage to a small region, which is beneficial for the host. Most Mtb-infected people will contain TB infection at this step and be asymptomatic (latent TB). In the case of the bacteria, the granuloma maintains the pathogen in a state of dormancy avoiding clearance by the immune system (Park et al., 2003). An efficient host protection against Mtb infection is associated with the induction, activation and proliferation of T helper 1 (Th1) cells (Cooper et al., 1993; Newport et al., 1996; Salgame, 2005). However, IFN-γ alone is not sufficient for the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Accordingly, cellular responses to Mtb induce IL-17 production, contributing to granuloma formation and control of bacterial growth (Cooper, 2010). However, excessive IL-17 levels exacerbate inflammation, increasing neutrophil recruitment and tissue damage (Lázár-Molnár et al., 2010). Despite the great steps made in the characterization of the acquired cellular response in TB patients, it remains to be elucidated what exactly constitutes a protective response or leads to disease pathology. Furthermore, how Mtb is able to evade host immune surveillance and persist is not fully clarified yet.Our Research Topic was launched on May 18th 2022 with a planned close on November 11th 2022, but it was extended until October 25th 2023 due to the flow of submissions.We are pleased to present a comprehensive Research Topic that delves into the intricate web of host-pathogen interactions during TB. Our Research Topic encompasses articles within a diverse range of disciplines, including cellular biology, endocrinology, host and bacterial genetics, epigenetics, immune regulation, immunometabolism, neuroimmunology, and aging. Through these multidisciplinary contributions, we aim to unravel the multifaceted dynamics underlying TB infection, shedding light on the disease’s diverse facets and offering valuable insights for researchers and healthcare professionals. We invite readers to explore the ever-evolving landscape of TB research and foster a deeper understanding of this global health challenge.