Glucose transporter expression differs between bovine monocyte and macrophage subsets and is influenced by milk production

Abstract

The peripartal period of dairy cows is characterized by negative energy balance and higher incidences of infectious diseases such as mastitis or metritis. With the onset of lactation, milk production is prioritized and large amounts of glucose are transported into the mammary gland. Decreased overall energy availability might impair the function of monocytes acting as key innate immune cells, which give rise to macrophages and dendritic cells and link innate and adaptive immunity. Information on glucose requirements of bovine immune cells is rare. Therefore, this study aims to evaluate glucose transporter expression of the 3 bovine monocyte subsets (classical, intermediate, and nonclassical monocytes) and monocyte-derived macrophages and to identify influences of the peripartal period. Blood samples were either collected from nonpregnant healthy cows or from 16 peripartal German Holstein cows at d -14, +7, and +21 relative to parturition. Quantitative real-time PCR was applied to determine mRNA expression of glucose transporters (GLUT) 1, GLUT3, and GLUT4 in monocyte subsets and monocyte-derived macrophages. The low GLUT1 and GLUT3 expression in nonclassical monocytes was unaltered during differentiation into macrophages, whereas in classical and intermediate monocytes GLUT expression was downregulated. Alternatively activated M2 macrophages consumed more glucose compared with classically activated M1 macrophages. The GLUT4 mRNA was only detectable in unstimulated macrophages. Neither monocytes nor macrophages were insulin responsive. In the peripartum period, monocyte GLUT1 and GLUT3 expression and the GLUT3/GLUT1 ratio were negatively correlated with lactose production. The high-affinity GLUT3 transporter appears to be the predominant glucose transporter on bovine monocytes and macrophages, especially in the peripartal period when blood glucose levels decline. Glucose transporter expression in monocytes is downregulated as a function of lactose production, which might impair monocyte to macrophage differentiation.

Integrated Metabolomics Study of the Milk of Heat-stressed Lactating Dairy Cows

“…Lactose is the predominant sugar in most species’ milk. The role of glucose metabolism in milk production is to transport glucose from the blood into the mammary gland for lactose synthesis, and has a vital function in milk yield relating to the osmoregulation of milk 23 24 . Although the present study did not identify significant differences in the milk lactose concentrations between the HS and HS-free groups, the milk yields of the HS group were greatly reduced ( Supplementary Table S4 ) relative to the HS-free group ( P < 0.01).…”

Lactation stage impacts the glycolytic function of bovine CD4+ T cells during ex vivo activation

“…Upregulation of aerobic glycolysis in activated cells requires an increase in cellular glucose entry. Glucose transporters, Glut1 and Glut3, in monocytes and macrophages have been shown to be modulated by milk production postpartum 57 . As identified in murine T cells, Glut1, and to a lesser extent Glut3, are important in transporting glucose into the cell, with Glut1 being essential to activation and effector function 58 .…”

<b>Modelo de risco para mastite no pós-parto:</b> aspectos hematológicos e bioquímicos

“…Neste período há grande estresse para os animais, por ocorrerem alterações fisiológicas (FAGLIARI, et al, 1998;MEGLIA et al, 2005), hematológicas (KANEKO, 2008;BIRGEL JUNIOR, 2012, TODOROVIĆ;DAVIDOVIĆ, 2012SMITH, 2014, metabólicas (POGLIANI; BIRGEL JÚNIOR, 2007;MOREIRA et al, 2015) e imunológicas que acarretam em maior susceptibilidade a doenças ,infecciosas como mastite, metrite, além de alterações como deslocamento de abomaso, cetose e retenção de secundinas MOYES, 2012).…”

“…Assim como a glicose é primordial para o desenvolvimento fetal e para a produção de leite ela é a fonte de energia utilizada pelos leucócitos PMN ativos, macrófagos e linfócitos durante a inflamação, ela estimula a proliferação e diferenciação dos leucócitos além de incrementar a quimiotaxia e a fagocitose dos neutrófilos MOYES, 2012). Além disso, também é a principal fonte de energia para os monócitos, peças chaves da imunidade inata Eger et al, (2016), estas dão origem aos macrófagos, cuja capacidade fagocítica, a produção de IL-1β e a polarização de macrófagos depende diretamente da disponibilidade de glicose (EGER et al, 2016). Também existem dentro dos leucócitos PMN as chamadas "ilhas" de glicogênio associadas a grânulos bactericidas que são utilizadas para destruir as bactérias (PAAPE et al, 2003).…”