ADVANCES IN UNDERSTANDING HOW MYCOBACTERIUM TUBERCULOSIS ESCAPES INNATE IMMUNE DEFENSES

Аннотация:

Mycobacterium tuberculosis (Mtb) is a highly adapted intracellular pathogen responsible for tuberculosis (TB), which continues to rank as one of the foremost infectious causes of mortality worldwide. The initial interplay between Mtb and the host’s innate immune system is critical in determining whether infection becomes established and how the disease progresses. Following entry into host cells, Mtb is recognized by diverse innate immune receptors that trigger multiple cellular defense responses. Nevertheless, Mtb has evolved sophisticated strategies to modulate and subvert these early immune mechanisms, enabling its survival and persistence. This review highlights recent advances in understanding the role of cytosolic nucleic acid–sensing pathways at the host–Mtb interface and outlines newly discovered mechanisms by which Mtb evades innate immune processes, including the regulation of membrane trafficking, membrane integrity, programmed cell death, and autophagy. Furthermore, we examine emerging insights into how Mtb manipulates key molecular regulatory systems within host cells—such as nuclear regulatory networks, the ubiquitin pathway, and intrinsic cellular immune factors—to neutralize host defenses. Enhanced knowledge of these innate immune evasion strategies will deepen our understanding of TB pathogenesis and support the development of next-generation vaccines and therapeutics.