TY - JOUR
T1 - Molecular determinants of disease severity in urinary tract infection
AU - Ambite, Ines
AU - Butler, Daniel
AU - Wan, Murphy Lam Yim
AU - Rosenblad, Therese
AU - Tran, Thi Hien
AU - Chao, Sing Ming
AU - Svanborg, Catharina
PY - 2021
Y1 - 2021
N2 - The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.
AB - The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.
U2 - 10.1038/s41585-021-00477-x
DO - 10.1038/s41585-021-00477-x
M3 - Review article
C2 - 34131331
AN - SCOPUS:85107905228
VL - 18
SP - 468
EP - 486
JO - Nature Reviews Urology
JF - Nature Reviews Urology
SN - 1759-4820
IS - 8
ER -