TY - JOUR
T1 - What is a host? Attributes of individual susceptibility
AU - Casadevall, Arturo
AU - Pirofski, Liise anne
N1 - Funding Information:
A.C. is supported by NIH grants AI033142, AI052733, and HL059842. L.P. is supported by NIH grants AG045044, AI097096, and AI123654.
Publisher Copyright:
© 2018 American Society for Microbiology.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - In every epidemic some individuals become sick and some may die, whereas others recover from illness and still others show no signs or symptoms of disease. These differences highlight a fundamental question of microbial pathogenesis: why are some individuals susceptible to infectious diseases while others who acquire the same microbe remain well? For most of human history, the answer assumed the hand of providence. With the advent of the germ theory of disease, the focus on disease causality became the microbe, but this did not explain how there can be different outcomes of infection in different individuals with the same microbe. Here we examine the attributes of susceptibility in the context of the "damage-response framework" of microbial pathogenesis. We identify 11 attributes that, although not independent, are sufficiently distinct to be considered separately: microbiome, inoculum, sex, temperature, environment, age, chance, history, immunity, nutrition, and genetics. We use the first letter of each to create the mnemonic MISTEACHING, underscoring the need for caution in accepting dogma and attributing disease causality to any single factor. For both populations and individuals, variations in the attributes that assemble into MISTEACHING can create an enormity of combinations that can in turn translate into different outcomes of host-microbe encounters. Combinatorial diversity among the 11 attributes makes identifying "signatures" of susceptibility possible. However, with their inevitable uncertainties and propensity to change, there may still be a low likelihood for prediction with regard to individual host-microbe interactions, although probabilistic prediction may be possible.
AB - In every epidemic some individuals become sick and some may die, whereas others recover from illness and still others show no signs or symptoms of disease. These differences highlight a fundamental question of microbial pathogenesis: why are some individuals susceptible to infectious diseases while others who acquire the same microbe remain well? For most of human history, the answer assumed the hand of providence. With the advent of the germ theory of disease, the focus on disease causality became the microbe, but this did not explain how there can be different outcomes of infection in different individuals with the same microbe. Here we examine the attributes of susceptibility in the context of the "damage-response framework" of microbial pathogenesis. We identify 11 attributes that, although not independent, are sufficiently distinct to be considered separately: microbiome, inoculum, sex, temperature, environment, age, chance, history, immunity, nutrition, and genetics. We use the first letter of each to create the mnemonic MISTEACHING, underscoring the need for caution in accepting dogma and attributing disease causality to any single factor. For both populations and individuals, variations in the attributes that assemble into MISTEACHING can create an enormity of combinations that can in turn translate into different outcomes of host-microbe encounters. Combinatorial diversity among the 11 attributes makes identifying "signatures" of susceptibility possible. However, with their inevitable uncertainties and propensity to change, there may still be a low likelihood for prediction with regard to individual host-microbe interactions, although probabilistic prediction may be possible.
KW - Host resistance
KW - Pathogenesis
KW - Virulence
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U2 - 10.1128/IAI.00636-17
DO - 10.1128/IAI.00636-17
M3 - Short survey
C2 - 29084893
AN - SCOPUS:85041007867
SN - 0019-9567
VL - 86
JO - Infection and immunity
JF - Infection and immunity
IS - 2
M1 - e00636-17
ER -