The Prospect of Nanoparticle Systems for Modulating Immune Cell Polarization During Central Nervous System Infection

Abstract

The blood-brain barrier (BBB) selectively restricts the entry of molecules from peripheral circulation into the central nervous system (CNS) parenchyma. Despite this protective barrier, bacteria and other pathogens can still invade the CNS, often as a consequence of immune deficiencies or complications following neurosurgical procedures. These infections are difficult to treat since many bacteria, such as Staphylococcus aureus, encode a repertoire of virulence factors, can acquire antibiotic resistance, and form biofilm. Additionally, pathogens can leverage virulence factor production to polarize host immune cells towards an anti-inflammatory phenotype, leading to chronic infection. The difficulty of pathogen clearance is magnified by the fact that antibiotics and other treatments cannot easily penetrate the BBB, which requires extended regimens to achieve therapeutic concentrations. Nanoparticle systems are rapidly emerging as a promising platform to treat a range of CNS disorders. Nanoparticles have several advantages, as they can be engineered to cross the BBB with specific functionality to increase cellular and molecular targeting, have controlled release of therapeutic agents, and superior bioavailability and circulation compared to traditional therapies. Within the CNS environment, therapeutic actions are not limited to directly targeting the pathogen, but can also be tailored to modulate immune cell activation to promote infection resolution. This perspective highlights the factors leading to infection persistence in the CNS and discusses how novel nanoparticle therapies can be engineered to provide enhanced treatment, specifically through modulation of immune cell polarization.

Bacterial meningitis in Africa

“…Bacterial infections of the brain are life-threatening because the brain is not easy to be reached by antibiotics because the BBB acts as a barrier between the brain and the systemic circulation (11). Nevertheless, death from bacterial meningitis does not occur because of the infection per se; the severe neuroinflammatory process that the host triggers in response to the infection results in the host's killer (12)(13)(14)(15).…”

“…Microglia reactive states are sometimes divided into pro-inflammatory M1-like “classically activated” and phagocytic M2-like “alternatively activated”; however, this classification is an oversimplification since microglial cells can present a large variety of functional phenotypes ( 80 ). The M1-like skewed microglial response is the typical hallmark of neuroinflammation in the pathophysiology of bacterial meningitis ( 11 , 72 ). Activated microglia release various cytokines and chemokines and acquire migratory, proliferative, and phagocytic properties ( 12 ).…”

Immunomodulatory and Antiprotozoal Potential of Fabricated Sesamum radiatum Oil/Polyvinylpyrrolidone/Au Polymeric Bionanocomposite Film

“…Recently, inflammation played a key role in the development and seriousness of neurodegenerative disorders such as Parkinson, Alzheimer, and multiple sclerosis diseases. Astrocytes and microglia are responsible for mediating the immunoresponse towards inflammatory agents in the central nervous system [52]. The essential oils are well-known lipophilics and contain organic molecules, which have the ability to transfer across the epithelium and move into systematic circulation to cross the blood-brain barrier and could preserve both neuropathological and behavioral impairments [53,54].…”