C3 Opsonization of Anthrax Bacterium and Peptidoglycan Supports Recognition and Activation of Neutrophils

• Published in: Microorganisms (Basel) Vol. 8; no. 7; p. 1039
• Main Authors: Popescu, Narcis I, Keshari, Ravi S, Cochran, Jackie, Coggeshall, K Mark, Lupu, Florea
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.07.2020; MDPI
• Subjects: Affinity; Anaphylatoxins; Anthrax; Bacillus anthracis; Bacteria; Cell activation; Cell culture; Cell walls; Cloning; Complement; Complement component C3; Complement component C5; Complement component C5a; Complement receptors; Degranulation; Deposition; Flow cytometry; Gram-positive bacteria; Health aspects; Health risks; Infections; Ingestion; Leukocytes (neutrophilic); Neutrophils; Opsonization; Pathogens; peptidoglycan; Peptidoglycans; Phagocytes; Risk reduction; Sepsis; Spores; Studies; Systemic diseases; Virulence; United States; St Louis Missouri; United States > US; C3; Bacillus anthracis; peptidoglycan; complement; anthrax; neutrophils
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms8071039

Neutrophils are the most abundant innate cell population and a key immune player against invading pathogens. Neutrophils can kill both bacterium and spores of , the causative anthrax pathogen. Unlike interactions with professional phagocytes, the molecular recognition of anthrax by neutrophils is largely unknown. In this study, we investigated the role of complement C3 deposition on anthrax particles for neutrophil recognition of bacterium and/or its cell wall peptidoglycan, an abundant pathogen-associated molecular pattern that supports anthrax sepsis. C3 opsonization and recognition by complement receptors accounted for 70-80% of the affinity interactions between neutrophils and anthrax particles at subphysiologic temperatures. In contrast, C3 supported up to 50% of the anthrax particle ingestion under thermophysiologic conditions. Opsonin-dependent low affinity interactions and, to a lower extent, opsonin-independent mechanisms, provide alternative entry routes. Similarly, C3 supported 58% of peptidoglycan-induced degranulation and, to a lower extent, 23% of bacterium-induced degranulation. Interestingly, an opsonin independent mechanism mediated by complement C5, likely through C5a anaphylatoxin, primes azurophilic granules in response to anthrax particles. Overall, we show that C3 deposition supports anthrax recognition by neutrophils but is dispensable for pathogen ingestion and neutrophil degranulation, highlighting immune recognition redundancies that minimize the risk of pathogen evasion.