Editorial: Innate immune response and interaction with adaptive immunity: role in tuberculosis immunology/vaccinology

resource-intensive nature of current treatments poses significant threats to adherence and disease outcomes while simultaneously adding to the growing issue of antibiotic resistance.Novel immunotherapeutic strategies are long overdue, given that new technologies and insights from other chronic diseases are available today. Innate immune cells are among the first to be affected during TB infection (4), and their molecular interactions with both bacilli and adaptive immune cells are scarcely understood yet critical to advance TB prevention or enhance treatment outcomes. To target it, it is crucial to first deepen our understanding of immune responses in the context of TB prevention, infection, and progression (or non-progression) to active TB disease while elucidating the mechanisms for extensive heterogeneity in immune responses among different hosts.There is immense potential in targeting these cells with creative methodologies. Zhao et al. present knowledge gaps by innate cell type, outlining areas for future investigation that could shed light on potential Host-Directed Therapy (HDT) targets. HDT targets the host immune response rather than the pathogen and can overcome issues such as drug resistance. Still, innate immune cells' physiology is more complicated than that since they can be a double-edged sword when infected with Mtb. Although neutrophil degranulation is meant to target the offending pathogen, this process may destroy neighboring cells and cause tissue dissolution (5,6). Mtb can skew macrophages towards metabolic states that permit bacterial growth and encourage chronic infection, yet precise mechanisms of macrophage plasticity and subset establishment in TB require further study (7). Dendritic cell differentiation is evident to be affected by Mtb since specific Mtb antigens induce altered differentiation, suppress maturation, and increase the expression of their inhibitory molecules (8,9,10), leading to reduced function. Lastly, Zhao et al. note that natural killer cells are suppressed during Mtb infection, but this process is another area where mechanistic knowledge is scarce. This review also highlights the importance of considering comorbidities and TB risk factors such as diabetes mellitus when studying how differences in host innate immunity contribute to disease outcomes. This is useful not only for insights into molecular mechanisms that make specific populations more susceptible to TB but also for designing therapies specific for certain at-risk populations.