Figure 3. Schematic illustration of the role of NO in Mtb disease.

Mtb infection upregulates the expression of iNOS, which catalyzes the conversion of L-arginine into L-citrulline and NO. NO-mediated Mtb killing and modulation of host immune and inflammatory responses are crucial for host protection against Mtb infection. On the other hand, NO reacts with O₂^•− to produce ONOO⁻ via NADPH oxidase. ONOO⁻ is pro-inflammatory, pro-oxidant and a potent suppressor of T-cell responses and its overproduction leads to host tissue damage and increased disease pathology. NO also plays important roles in Mtb physiology where it is sensed by the Mtb heme sensor kinase proteins DosS and DosT, which activate the response regulator DosR thereby inducing the Mtb dormancy regulon. Also, NO can be converted to NO₂⁻ or NO₃⁻, which arrest Mtb growth and lead to transcriptional adaptation of Mtb stress-associated genes.