The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease

Fairbairn, Lynsey; Kapétanovic, Ronan; Sester, David P.; Hume, David

doi:10.1189/jlb.1110607

Cited by 160 publications

(146 citation statements)

References 244 publications

(228 reference statements)

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“…We and others have shown that pig monocytes can also be separated into subpopulations that differ in their expression of CD16 and the scavenger receptor CD163 (21). As shown in Fig.…”

Section: Pig Bmdm Display Appropriate Marker Expression For Macrophagmentioning

confidence: 88%

“…CD16, Fc receptor 3, was also expressed at high levels on all cells, as was SCW3a and CD172 (SIRP a). The pig BMDM had almost undetectable expression of CD163 and in that respect resembled more mature pig (21) and human (41) monocyte subsets.…”

Section: Pig Bmdm Display Appropriate Marker Expression For Macrophagmentioning

confidence: 99%

“…However, CSF-1 signals rather differently in humans than in mice (20); numerous differences have been observed in the responses of the two species to LPS and the sets of innate immune effectors (21). The immunityrelated GTPase family provides one example, as follows: mice possess 23 different members, whereas only one can be found in humans (22).…”

mentioning

confidence: 99%

“…We recently reviewed the differences between mouse and human inflammatory biology in the context of consideration of the domestic pig as an alternative model (21). The comparison is somewhat compromised by the use of distinct populations of cells.…”

mentioning

confidence: 99%

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Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide

Kapétanovic

Fairbairn

Beraldi

et al. 2012

The Journal of Immunology

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118

133

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Mouse bone marrow-derived macrophages (BMDM) grown in M-CSF (CSF-1) have been used widely in studies of macrophage biology and the response to TLR agonists. We investigated whether similar cells could be derived from the domestic pig using human rCSF-1 and whether porcine macrophages might represent a better model of human macrophage biology. Cultivation of pig bone marrow cells for 5–7 d in presence of human rCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, and CD172a), were potent phagocytic cells, and produced TNF in response to LPS. Pig BMDM could be generated from bone marrow cells that had been stored frozen and thawed so that multiple experiments can be performed on samples from a single animal. Gene expression in pig BMDM from outbred animals responding to LPS was profiled using Affymetrix microarrays. The temporal cascade of inducible and repressible genes more closely resembled the known responses of human than mouse macrophages, sharing with humans the regulation of genes involved in tryptophan metabolism (IDO, KYN), lymphoattractant chemokines (CCL20, CXCL9, CXCL11, CXCL13), and the vitamin D3-converting enzyme, Cyp27B1. Conversely, in common with published studies of human macrophages, pig BMDM did not strongly induce genes involved in arginine metabolism, nor did they produce NO. These results establish pig BMDM as an alternative tractable model for the study of macrophage transcriptional control.

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“…We and others have shown that pig monocytes can also be separated into subpopulations that differ in their expression of CD16 and the scavenger receptor CD163 (21). As shown in Fig.…”

Section: Pig Bmdm Display Appropriate Marker Expression For Macrophagmentioning

confidence: 88%

Section: Pig Bmdm Display Appropriate Marker Expression For Macrophagmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide

Kapétanovic

Fairbairn

Beraldi

et al. 2012

The Journal of Immunology

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118

133

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“…We chose pigs for our model of sirs after cpB because aside from the similarities in their immune systems, porcine physiology is also close to that of humans, making them a widely used model in medicine 9 . in fact, pigs are more sensitive to cpB and cardioplegic arrest than humans, whereas they are more tolerant of endotoxins.…”

Section: Discussionmentioning

confidence: 99%

Systemic inflammatory response syndrome is reduced by preoperative plasma-thrombo-leukocyte aphaeresis in a pig model of cardiopulmonary bypass

et al. 2016

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Objectives. The systemic inflammatory response syndrome (SIRS) after cardiac surgery with cardiopulmonary bypass (CPB) exacerbates organ dysfunction and increases postoperative mortality. The aim of this study was to reduce SIRS after CPB in a pig model by profoundly decreasing all blood defence factors (complement, coagulation and fibrinolytic and contact systems, leukocytes and thrombocytes) using pre-operative aphaeresis. Methods. Thirty-three pigs underwent 3 h of hypothermic CPB with 2 h of cardioplegic arrest, followed by 4 days of observation. One half of the sample underwent prebypass plasma-thrombo-leukocyte aphaeresis with the adjuvant leukofiltration. Results. In the control group, there were classical signs of SIRS (tachycardia, tachypnea and leukocytosis) postoperatively. There was also myocardial ischaemia and the need for inotropic support in 90% of the control animals. Neutrophils showed an increase in superoxide anion production (P < 0.001), and surface neutral protease activity (P < 0.001) and blood endotoxin levels increased (P < 0.01) compared with preoperative levels. In contrast, in the aphaeretic group, there were no classical signs of SIRS; no myocardial ischaemia; minimum neutrophil production of the superoxide anion and protease activity were recorded (P < 0.001); and endotoxin levels were also decreased (P < 0.05) compared with the controls. In the control group, the haemodynamic problems associated with disconnecting from CPB correlated with the histologic findings in the myocardium (leukocyte endothelial adhesion and leukodiapedesis). Conclusions. Pre-operative plasma-thrombo-leukocyte aphaeresis significantly reduces the major symptoms of SIRS and organ dysfunction after 3 h of CPB without adverse effects, such as bleeding and infection, during the postoperative course.

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Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia

Shih

Brown

Barrington

et al. 2022

Glia

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Microglia play key roles in brain homeostasis as well as responses to neurodegeneration and neuroinflammatory processes caused by physical disease and psychosocial stress. The pig is a physiologically relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs are an important agricultural species, and there is a need to understand how microglial function affects their welfare. As a basis for improved understanding to enhance biomedical and agricultural research, we sought to characterize pig microglial identity at genome-wide scale and conduct inter-species comparisons. We isolated pig hippocampal tissue and microglia from frontal cortex, hippocampus, and cerebellum, as well as alveolar macrophages from the lungs and conducted RNAsequencing (RNAseq). By comparing the transcriptomic profiles between microglia, macrophages, and hippocampal tissue, we derived a set of 239 highly enriched genes defining the porcine core microglial signature. We found brain regional heterogeneity based on 150 genes showing significant (adjusted p < 0.01) regional variations and that cerebellar microglia were most distinct. We compared normalized gene expression for microglia from human, mice and pigs using microglia signature gene lists derived from each species and demonstrated that a core microglial marker gene signature is conserved across species, but that species-specific expression subsets also exist. Our data provide a valuable resource defining the pig microglial transcriptome signature that validates and highlights pigs as a useful large animal species bridging between rodents and humans in which to study the role of microglia during homeostasis and disease.

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The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease

Cited by 160 publications

References 244 publications

Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide

Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide

Systemic inflammatory response syndrome is reduced by preoperative plasma-thrombo-leukocyte aphaeresis in a pig model of cardiopulmonary bypass

Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia

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