Table 5.

BBB-breaching pathogenic infections and associated immunomodulatory activity.

Pathogen	Mode of Pathogenesis	Immunological Factors Contributing BBB Infection	References
A. baumannii	-Meningitis -Catheter-associated infection	Increased inflammatory cell response, toll-like receptor (TLR) altered expression, and proinflammatory cytokine burst within 24 h of infection	[142,143]
E. coli	-Endothelial cells -Attenuation of transforming growth factor (TGF)-β 1 signaling	Increased expression of endothelial-derived platelet-derived growth factor receptor (PDFGR) and intercellular adhesion molecule (ICAM), resulting in inflammation	[144]
H. influenzae	-Large amount of vascular endothelial growth factor receptor (VEGFR) -Adenosine receptor dysfunction	Endothelial disruption and tight junction altered expression: downregulation of tumor necrosis factor (TNF-α); endothelial proliferation	[145,146]
K. pneumoniae	-Cerebrospinal infection -Intracranial infection	Increased production of proinflammatory cytokines and chemokines; induction of hypoxia inducible factor (HIF)-1α	[147]
L. monocytogenes	-Vimentin-mediated infection Neuroinflammation	In1F virulent factor-associated downregulation of tight junction and overexpression of PDFGR and ICAM, resulting in inflammation	[148]
N. meningitidis	-Secretion of IgA protease -Evasion of immune response	Deformation of adherence junction, triggering IL-6 and IL-8 expression: leukocyte infiltration and infected phagocyte movement	[149,150]
P. aeruginosa	-Cerebrospinal infection -Meningitis	Increased production of inflammatory cell response; overproduction of IL-1β and IL-6	[151]
S. aureus	-Brain abscesses and endocarditis -Cytokine burst	Stimulate immune invasion, T cell activation: burst of proinflammatory cytokines; TNF-α, IL-6, and IL-10 overproduction	[152]
S. pneumoniae	-Neonatal meningitis -Laminin receptor transcytosis	TNF-α, IL-6, and IL-10 overproduction and increased permeability through anchored tight junction; cleavage of IgA through pneumococci IgA protease	[153,154]