TY - JOUR
T1 - Fighting the monster
T2 - Applying the host damage framework to human central nervous system infections
AU - Panackal, Anil A.
AU - Williamson, Kim C.
AU - van de Beek, Diederik
AU - Boulware, David R.
AU - Williamson, Peter R.
N1 - Publisher Copyright:
© 2016 Panackal et al.
PY - 2016/1/26
Y1 - 2016/1/26
N2 - 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 sizerestricted 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.
AB - 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 sizerestricted 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.
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U2 - 10.1128/mBio.01906-15
DO - 10.1128/mBio.01906-15
M3 - Review article
C2 - 26814182
AN - SCOPUS:84960153134
SN - 2161-2129
VL - 7
JO - mBio
JF - mBio
IS - 1
M1 - e01906-15
ER -