Aging associated altered response to intracellular bacterial infections and its implication on the host

https://doi.org/10.1016/j.bbamcr.2021.119063Get rights and content
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Highlights

  • Several anti-microbial factors are elevated in senescent cells resulting in reduced intracellular bacterial.

  • Nitric Oxide plays a pivotal role in limiting infection in senescent cells and is negatively regulated by p38 MAPK.

  • Similarly, high nitrosative and pro-inflammatory responses decrease bacterial infection in old mice.

  • But a deficient host-protective anti-inflammatory response results in infection-induced mortality of old mice.

Abstract

The effects of senescence on geriatric disorders are well explored, but how it influences infections in the elderly is poorly addressed. Here, we show that several anti-microbial responses are elevated in senescent epithelial cells and old mice, which results in decreased bacterial survival in the host after infection. We identify higher levels of iNOS as a crucial host response and show that p38 MAPK in senescent epithelial cells acts as a negative regulator of iNOS transcription. However, in older mice, the ability to impede bacterial infection does not result in enhanced survival, possibly because elevated pro-inflammatory responses are not countered by a robust host protective anti-inflammatory response. Overall, while addressing an alternate advantage of senescent cells, our study demonstrates that infection-associated morbidity in the elderly may not be the sole outcome of pathogen loads but may also be influenced by the host's ability to resolve inflammation-induced damage.

Keywords

Aging
Infection
Senescence, Salmonella
Tuberculosis
Nitric oxide

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