**1. Introduction**

Known as one of the first responder cells of the innate immune system, neutrophils are described as phagocytes in textbooks that are involved in initial early host-defence responses during infection/injury. However, the discovery of neutrophil extracellular traps (NETs) has shifted the paradigm of our current understanding of neutrophil functions, and their significance during immune responses, quite drastically. Upon interaction with an invading microbe/cytokine, neutrophils release their chromatin material together with a wide range of granular enzymes to form net-like structures known as NETs [1]. NETs cannot only trap the invading pathogen but also degrade them with NET-associated proteolytic enzymes [1]. NETs are involved in numerous infectious/non-infectious diseases and are believed to be crucially involved during inflammation. While NETs are beneficial during infections, they may play a detrimental role in the case of inflammation, autoimmunity and other pathophysiological conditions. NETs accelerate the inflammatory processes by releasing a wide range of active molecules like danger associated molecular patterns (DAMPs), histones, as well as active lytic-enzymes in extracellular space, leading to further immune responses. NETs, therefore, also may serve as a potential source

of auto-antigens against which the autoantibodies associated with a wide range of inflammatory autoimmune diseases are directed.

The functions and morphology of neutrophils undergo radical transformation during inflammation, injury and infection. Neutrophils migrate along vesicles by expressing a wide range of migratory protein cascades as well as start to express various pattern recognition receptors and secrete a wide range of cytokines in a process called 'neutrophil activation'. Over the years, it has become clearer that only a fraction of neutrophils can make NETs, indicating the heterogeneity of the neutrophil population, especially during sterile inflammation [2,3] Therefore, it is important to speculate if only a specific subpopulation of neutrophils can undergo NET formation [2,4]. A distinct population of low-density neutrophils, for example, are known to be more vulnerable towards NET formation in systemic lupus erythematosus (SLE) patients [3,5], possibly explaining a link between this disease and NET formation. Interestingly, the composition of NETs may differ based on the stimuli and, therefore, the disease with which it is associated [6]. Furthermore, in certain situations, NETs also might have anti-inflammatory characteristics [7]. It is, therefore, important to characterize NETs in a disease-specific manner to understand their specific involvement during the development of autoimmunity and disease.
