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Mitochondrial perturbations in low-protein-diet-fed mice are associated with altered neutrophil development and effector functions.

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.

SUBMITTER: Thind MK

PROVIDER: S-EPMC11372442 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Mitochondrial perturbations in low-protein-diet-fed mice are associated with altered neutrophil development and effector functions.

Thind Mehakpreet K MK Miraglia Emiliano E Ling Catriona C Khan Meraj A MA Glembocki Aida A Bourdon Celine C ChenMi YueYing Y Palaniyar Nades N Glogauer Michael M Bandsma Robert H J RHJ Farooqui Amber A

Cell reports 20240718 8

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 ...[more]

PMID: 39028622

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Project description:IntroductionFeeding low protein (LP) diet to animals impose severe challenge to animals' immune homeostasis. However, limited knowledge about the underlying adaption mechanism of host and ruminal microbiota responding to LP diet were well understood. Herein, this study was performed to examine the changes in relative abundance of ruminal microbiota and host ruminal mucosal transcriptome profiles in response to a LP diet.MethodsA total of twenty-four female Xiangdong balck goats with similar weight (20.64 ± 2.40 kg) and age (8 ± 0.3 months) were randomly assigned into two groups, LP (5.52% crude protein containing diet) and CON (10.77% crude protein containing diet) groups. Upon completion of the trial, all goats were slaughtered after a 16-hour fasting period in LiuYang city (N 28°15', E 113°63') in China. HE staining, free amino acids measurement, transcriptome analysis and microbiome analysis were applied to detect the morphology alterations, free amino acids profile alterations and the shift in host ruminal mucosal transcriptome and ruminal microbiota communities.ResultsFirstly, the results showed that feeding LP diet to goats decreased the rumen papilla width (P = 0.043), surface area (P = 0.013) and total ruminal free amino acids concentration (P = 0.016). Secondly, microbiome analysis indicated that 9 microbial genera, including Eubacterium and Prevotella, were enriched in LP group while 11 microbial genera, including Butyrivibrio and Ruminococcus, were enriched in CON group. Finally, in terms of immune-related genes, the expression levels of genes involved in tight junction categories (e.g., MYH11, PPP2R2C, and MYL9) and acquired immunity (e.g., PCP4 and CXCL13) were observed to be upregulated in the LP group when compared to the CON group.ConclusionUnder the LP diet, the rumen exhibited increased relative abundance of pathogenic microbiota and VFA-degrading microbiota, leading to disruptions in immune homeostasis within the host's ruminal mucosa. These findings indicate that the ruminal microbiota interacts with host results in the disruption in animals' immune homeostasis under LP diet challenge.

Dataset Information

Mitochondrial perturbations in low-protein-diet-fed mice are associated with altered neutrophil development and effector functions.

Publications

Mitochondrial perturbations in low-protein-diet-fed mice are associated with altered neutrophil development and effector functions.

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