Mitochondrial perturbations in low-protein-diet-fed mice are associated with altered neutrophil development and effector functions.
Cell Rep
; 43(8): 114493, 2024 Jul 18.
Article
en En
| MEDLINE
| ID: mdl-39028622
ABSTRACT
Severe malnutrition is associated with infections, namely lower respiratory tract infections (LRTIs), diarrhea, and sepsis, and underlies the high risk of morbidity and mortality in children under 5 years of age. Dysregulations in neutrophil responses in the acute phase of infection are speculated to underlie these severe adverse outcomes; however, very little is known about their biology in this context. Here, in a lipopolysaccharide-challenged low-protein diet (LPD) mouse model, as a model of malnutrition, we show that protein deficiency disrupts neutrophil mitochondrial dynamics and ATP generation to obstruct the neutrophil differentiation cascade. This promotes the accumulation of atypical immature neutrophils that are incapable of optimal antimicrobial response and, in turn, exacerbate systemic pathogen spread and the permeability of the alveolocapillary membrane with the resultant lung damage. Thus, this perturbed response may contribute to higher mortality risk in malnutrition. We also offer a nutritional therapeutic strategy, nicotinamide, to boost neutrophil-mediated immunity in LPD-fed mice.
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Base de datos:
MEDLINE
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En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Kenia