title: Fighting the Monster: Applying the Host Damage Framework to Human Central Nervous System Infections.
abstract: The host damage-response framework states that microbial pathogenesis is a product of microbial virulence factors and collateral damage from host immune responses. Immune-mediated host damage is particularly important within the size-restricted central nervous system (CNS), where immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. In this review, we compare human host and therapeutic responses in representative nonviral generalized CNS infections that induce archetypal host damage responses: cryptococcal menigoencephalitis and tuberculous meningitis in HIV-infected and non-HIV-infected patients, pneumococcal meningitis, and cerebral malaria. Consideration of the underlying patterns of host responses provides critical insights into host damage and may suggest tailored adjunctive therapeutics to improve disease outcome.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Panackal
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Kim C
authors.initials: KC
authors.lastname: Williamson
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA williamsonpr@mail.nih.gov.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Williamson
mesh_terms: D002494:Central Nervous System Infections / Q000473:pathology*; D003454:Cryptococcus / Q000276:immunology* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D009161:Mycobacterium / Q000276:immunology* / Q000472:pathogenicity; D010961:Plasmodium / Q000276:immunology* / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity
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