**5. Debilitated neutrophils**

The quick release of ROS and the presence of pre-formed proteolytic granules make neutrophils one of the first phagocytic cells to reach infection sites. Clinically, the majority of infected cells in patients with active tuberculosis' sputum and bronchoalveolar lavage are neutrophils. The results of in vitro research on neutrophils' capacity to kill *M. tuberculosis* and *B. pseudomallei* vary, which is likely due to a variety of host- and organism-specific variables as well as variations in experimental methodology [29]. Unstimulated neutrophils in diabetics have been shown to produce more inflammatory cytokines and ROS, which has been linked to AGE-direct activation. However, in diabetic hosts, neutrophil responses to infection seem to be primarily inhibited. Reduced glucose metabolism via the pentose-phosphate route, which generates NADPH, a need for adequate NADPH oxidase function, may be linked to decreased pathogen-stimulated ROS generation [28]. Furthermore, neutrophil dysfunction in diabetic hosts may be caused by diminished glutathione reductase activity, which also controls neutrophil-based ROS generation and phagocytosis. ROS induces the release of neutrophil extracellular traps (NET), another significant bactericidal mechanism in addition to directly killing germs. Such deficiencies in neutrophil function might make it easier for internal bacteria to use neutrophils as a haven and a vehicle for spreading in diabetic hosts [34].

Following stimulation with phorbol 12-myristate-13-acetate, isolated neutrophils from T2D TB patients produced less ROS. Increased resistin levels in the blood of T2D patients were linked to this ROS generation deficiency [35]. When exposed to a high glucose content media, isolated neutrophils from healthy patients suppressed superoxide (O2−). Through the suppression of glucose-6-phosphate dehydrogenase (G6PD), which interfered with nicotinamide adenine dinucleotide phosphate synthesis, this impairment was caused.

When healthy individuals' blood was exposed to bacterial wall components after becoming hyperglycemic the blood's neutrophil degranulation reduces. Another example of neutrophil dysfunction in *S. aureus* phages was provided by C3-mediated complement suppression brought on by hyperglycemia [36]. It is reported that NETs, which increase susceptibility to infections, are less likely to form when hyperglycemia is present. All of these studies showed that hyperglycemia causes neutrophil dysfunction, which includes irregularities in ROS production, impairments in neutrophil degranulation, inhibition of immunoglobulin-mediated opsonization decreased phagocytosis, and errors in NET formation.
