Comparison of gene expression profiles between human and mouse monocyte subsets

Abstract

Blood of both humans and mice contains 2 main monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 270 genes in humans and 550 genes in mice were differentially expressed between subsets by 2-fold or more. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous of these differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the 2 species' subsets, including CD36, CD9, and TREM-1. Other differences included a prominent peroxisome proliferatoractivated receptor ␥ (PPAR␥) signature in mouse monocytes, which is absent in humans, and strikingly opposed patterns of receptors involved in uptake of apoptotic cells and other phagocytic cargo between human and mouse monocyte subsets. Thus, whereas human and mouse monocyte subsets are far more broadly conserved than currently recognized, important differences between the species deserve consideration when models of human disease are studied in mice. (Blood. 2010;115:e10-e19) IntroductionSubpopulations of blood monocytes exist in humans, mice, and other species. 1-4 CD14 ϩϩ CD16 Ϫ and CD14 ϩ CD16 ϩ cell surface protein signatures 2 identify and distinguish the 2 major human monocyte subsets. In wild-type mice, monocytes can be identified as CD115 ϩ (c-fms/macrophage colony-stimulating factor [M-CSF] receptor), CD11b ϩ , F4/80 int blood cells, with monocyte subsets distinguished as Ly-6C ϩ and Ly-6C lo cells. [4][5][6][7] Ly-6C is frequently identified by flow cytometry using the Gr-1 antibody, which recognizes an epitope of both Ly-6C and Ly-6G. 8 It should be noted that monocytes express only Ly-6C. 4,9 It has been proposed that CD14 ϩϩ CD16 Ϫ human monocytes (here called CD16 Ϫ monocytes), which comprise approximately 95% of human blood monocytes, are counterparts to CD115 ϩ Ly-6C ϩ mouse monocytes (here called Ly-6C ϩ monocytes), which comprise approximately 50% of circulating mouse monocytes. 2,3,6,7,10 Moreover, CD14 ϩ CD16 ϩ human monocytes (here called CD16 ϩ monocytes) and CD115 ϩ Ly-6C lo mouse monocytes (here called Ly-6C lo monocytes) appear to bear similarity. 2,3,6,7,10 These proposed similarities arise from evidence that differential expression patterns of certain molecules between the 2 major subsets are shared in humans and mice. Namely, chemokine receptors CCR1 and CCR2 are more highly expressed on CD16 Ϫ human and Ly-6C ϩ mouse monocytes at the mRNA or protein level, 3,11,12 whereas CX 3 CR1 is elevated on CD16 ϩ human and Ly-6C lo mouse monocytes. 3 In addition, CD11a (␣ L integrin; Itgal), CD62L, and CD43 are conserved in their differential expression between monocyte subsets in humans and mice. [2][3][4]10,13 Further, CD16, the signature marker for distinguishing human monocyte subsets, was recently observed on the surface of mouse Ly-6C lo , but not Ly-6C ϩ , monocytes. 14 CD11c (␣ x integrin; Itgax) is more highly expressed on CD16 ϩ human monocytes...

Human CD8+ T cells drive Th1 responses through the differentiation of TNF/iNOS‐producing dendritic cells

“…of homology between mouse and human monocyte subsets and that the mouse Ly6C hi CCR2 1 subset corresponds to the human classical subset [32]. Since Tip-DCs in mice have been shown to arise from Ly6C hi CCR2 1 monocytes [3,33], it is likely that TipDCs seen in our model arise mainly from the classical subset, especially since this population represents 90% of total blood monocytes.…”

Monocytes and Macrophages in Cancer: Development and Functions

“…However, the two subsets can also be distinguished by functions such as the patrolling behavior found in Ly6 low but not Ly6C high monocytes [18]. As these phenotypical and functional differences are found in both human and murine monocyte subsets, evolutionary conservation of monocyte heterogeneity has been suggested [19][20][21][22]. The developmental relationship between the monocyte subsets is still not completely understood [11].…”

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

“…Most human studies employ monocyte-derived macrophages grown in CSF-1 (24). Mouse monocytes are not readily accessed in substantial numbers and may differ from humans in terms of their maturation state/subpopulations (25) and in their response to inflammatory stimulus like LPS (26). Conversely, access to human bone marrow is also not straightforward, and human BMDM have not been reported.…”