Since complement deposition is aspecific its activation is guided by three recognition pathways, including the aforementioned classical complement pathway in which complement activation is triggered by the recognition of S. The complement system also comprises proteins that label bacterial surfaces that enhance phagocytosis. Furthermore, IgGs and IgMs induce phagocytosis indirectly, by activating the complement cascade via the classical pathway ( 13). Once bound to the bacteria, immunoglobulins of class G (IgG) and A (IgA) induce phagocytosis by direct interaction of their Fc with their specific phagocytic receptors FcγRs and FcαRs. Immunoglobulins are adaptive immune molecules designed to specifically recognize an antigen, such as Staphylococcal surface proteins. The main opsonins are immunoglobulins and complement proteins ( 12). This process is typically aided by opsonins, host plasma proteins that mark bacterial surfaces increasing their probability of interacting with neutrophils phagocytic receptors. Phagocytosis is an active process that requires the direct contact between S. These events, combined with the tuning of the vacuolar pH, finely regulates the enzymatic activity, ultimately leading to killing and digestion of the bacteria ( 10, 11). The phagosomes then mature into lytic vesicles: they become filled with antimicrobial substances stored into cytoplasmic granules and with toxic reactive oxygen species. Neutrophils mainly kill pathogens through phagocytosis, a process in which bacteria are engulfed into intracellular vesicles called phagosomes. The inflammatory milieu also primes neutrophils, boosting their capacity to recognize and clear bacteria ( 9). When S. aureus invades tissues, neutrophils sense inflammatory signals released by local cells and extravasate, migrating towards the site of infection ( 5– 8). These terminally differentiated cells are regularly released in the bloodstream to patrol the body.
#Flowjo 10 histogram percentage of max professional
Neutrophils are the most abundant professional phagocytes of the innate immune system. This suggests that studying the role of neutrophils in the clearance of different clinical strains of this bacterium could provide us with clues to develop therapies. Patients with compromised neutrophil function are more susceptible to S. Alternative measures such as vaccine candidates tested so far were unsuccessful ( 3, 4), thus new research efforts are urgently required. aureus infections is becoming increasingly difficult ( 2). Due to its fast acquisition of antibiotic resistance, treatment of S. Staphylococcus aureus is a leading pathogen causing an array of serious and possibly fatal diseases in humans ( 1). Our rapid assay to monitor phagocytosis can be used to study neutrophil deficiencies and bacterial evasion, but also provides a powerful tool to assess the opsonic capacity of antibodies, either in the context of natural immune responses or immune therapies. the tagging of microbial surfaces with plasma-derived host proteins like antibodies and complement. aureus is greatly enhanced by opsonization, i.e. We show that effective phagocytic uptake of S. Here we describe a robust and relatively high-throughput flow cytometry assay to quantify phagocytosis of S. These professional phagocytes rapidly migrate to the site of infection to engulf bacteria and destroy them via specialized intracellular killing mechanisms. Neutrophils play a key role in the human immune response to Staphylococcus aureus infections.
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