Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1.

Cytosolic detection of microbial products is essential for the initiation of an innate immune response against intracellular pathogens such as Mycobacterium tuberculosis (Mtb). During Mtb infection of macrophages, activation of cytosolic surveillance pathways is dependent on the mycobacterial ESX-1 secretion system and leads to type I interferon (IFN) and interleukin-1β (IL-1β) production. Whereas the inflammasome regulates IL-1β secretion, the receptor(s) responsible for the activation of type I IFNs has remained elusive.

Nucleic acid driven sterile inflammation.

The etiology of sterile inflammatory conditions is complex and affected by a variety of genetic, environmental and stochastic factors. But despite this overt complexity, progress has been made in elucidating mechanisms underlying disease pathogenesis. An intriguing new finding that has emerged over the past years was the realization that innate immune receptors participate in driving or aggravating disease manifestation.