Phenotypic and functional analysis of monocyte populations in cattle peripheral blood identifies a subset with high endocytic and allogeneic T-cell stimulatory capacity.

Yolanda Corripio-Miyar,Colin J Mcinnes,Kirsty Jensen,Elizabeth J Glass,Sean R Wattegedera,Gary Entrican,Jayne Hope,Yvonne Pang

doi:10.1186/s13567-015-0246-4

Yolanda Corripio-Miyar, Colin J Mcinnes + Show 6 more

Open Access

https://doi.org/10.1186/s13567-015-0246-4

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Abstract

Circulating monocytes in several mammalian species can be subdivided into functionally distinct subpopulations based on differential expression of surface molecules. We confirm that bovine monocytes express CD172a and MHC class II with two distinct populations of CD14+CD16low/-CD163+ and CD14−CD16++CD163low- cells, and a more diffuse population of CD14+CD16+CD163+ cells. In contrast, ovine monocytes consisted of only a major CD14+CD16+ subset and a very low percentage of CD14−CD16++cells. The bovine subsets expressed similar levels of CD80, CD40 and CD11c molecules and mRNA encoding CD115. However, further mRNA analyses revealed that the CD14−CD16++ monocytes were CX3CR1highCCR2low whereas the major CD14+ subset was CX3CR1lowCCR2high. The former were positive for CD1b and had lower levels of CD11b and CD86 than the CD14+ monocytes. The more diffuse CD14+CD16+ population generally expressed intermediate levels of these molecules. All three populations responded to stimulation with phenol-extracted lipopolysaccharide (LPS) by producing interleukin (IL)-1β, with the CD16++ subset expressing higher levels of IL-12 and lower levels of IL-10. The CD14−CD16++ cells were more endocytic and induced greater allogeneic T cell responses compared to the other monocyte populations. Taken together the data show both similarities and differences between the classical, intermediate and non-classical definitions of monocytes as described for other mammalian species, with additional potential subpopulations. Further functional analyses of these monocyte populations may help explain inter-animal and inter-species variations to infection, inflammation and vaccination in ruminant livestock.

Highlights

The innate immune system is the first line of host defense against pathogens, playing an important role during the early phase of infection
Ruminant blood contains cell populations with differential expression of CD14 and CD16 In order to identify myeloid cell populations in the peripheral blood of cattle, expression of CD14 and CD16 was analysed on PBMC (n = 6)
In order to further define the nature of the CD14+ and CD16+ populations, PBMC were double-labelled with anti-CD14 and anti-CD16 conjugated antibodies, a method commonly used to identify monocyte subsets in human blood [2,7,9,42]

Summary

Introduction

The innate immune system is the first line of host defense against pathogens, playing an important role during the early phase of infection. Myeloid cells are among the key mediators of the innate immune system and consist of heterogeneous populations with overlapping relationships and function between monocytes, macrophages and dendritic cells (DC) [1-3] These populations differ phenotypically and functionally from each other based on their tissue location and previous. The evidence derived mainly from mouse studies suggests that the classical monocyte population responds to cytokine and chemokine signals by entering sites of infection and differentiating into macrophages and dendritic cells, contributing to inflammation and resolution of the infection [2] These activities are reflected in human classical monocyte responses to TLR ligands which result in pro-inflammatory cytokine up-regulation, accompanied by release of interleukin (IL)-10, some studies suggest the intermediate monocyte population is the major IL-10 producing subset [11]. In contrast the non-classical population appears to be mainly involved in patrolling the endothelium of the blood vessels, expressing very little IL-10 and with high levels of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-α) [12,13]

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