Monocyte Subsets: Phenotypes and Function in Tuberculosis Infection.

Pavithra Sampath,Uma Devi Ranganathan,Ramalingam Bethunaickan,Kadar Moideen

doi:10.3389/fimmu.2018.01726

Pavithra Sampath, Uma Devi Ranganathan + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2018.01726

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Abstract

Monocytes are critical defense components that play an important role in the primary innate immune response. The heterogeneous nature of monocytes and their ability to differentiate into either monocyte-derived macrophages or monocyte-derived dendritic cells allows them to serve as a bridge between the innate and adaptive immune responses. Current studies of monocytes based on immunofluorescence, single-cell RNA sequencing and whole mass spectrometry finger printing reveals different classification systems for monocyte subsets. In humans, three circulating monocyte subsets are classified based on relative expression levels of CD14 and CD16 surface proteins, namely classical, intermediate and non-classical subsets. Transcriptomic analyses of these subsets help to define their distinct functional properties. Tuberculosis (TB) is a disease instigated by the deadly pathogen Mycobacterium tuberculosis. Current research on monocytes in TB has indicated that there are alterations in the frequency of intermediate and non-classical subsets suggesting their impact in bacterial persistence. In this review, we will focus on these monocyte subsets, including their classification, frequency distribution, cytokine profiles, role as a biomarker and will comment on future directions for understanding the salient phenotypic and functional properties relevant to TB pathogenesis.

Highlights

Mononuclear cells are professional phagocytes that are highly skilled in defense against many pathogens including Mycobacterium tuberculosis (MTB)
Human monocytes are bone marrow-derived leukocytes that circulate in the blood and can differentiate into monocyte-derived macrophages and monocyte-derived dendritic cells that govern innate and adaptive immune responses [1]
Non-classical monocytes exhibit upregulation in the mRNA levels of heme oxygenase 1 (HMOX1), Villin 2 (VIL2), and Src family kinases constituting hemopoietic cell kinase (HCK) and tyrosineprotein kinase Lyn (LYN) and protein levels of actin related proteins (ARP2 and ARP3), HCK and LYN. These proteins phosphorylate the immunoreceptor tyrosine-based activation motif (ITAM) of Fc receptors leading to recruitment of downstream genes necessary for cytoskeletal remodeling suggesting a role for this macrophage subset in Fc receptor-mediated phagocytosis [34]

Summary

INTRODUCTION

Mononuclear cells (monocytes/macrophages) are professional phagocytes that are highly skilled in defense against many pathogens including Mycobacterium tuberculosis (MTB). Non-classical monocytes exhibit upregulation in the mRNA levels of heme oxygenase 1 (HMOX1), Villin 2 (VIL2), and Src family kinases constituting hemopoietic cell kinase (HCK) and tyrosineprotein kinase Lyn (LYN) and protein levels of actin related proteins (ARP2 and ARP3), HCK and LYN These proteins phosphorylate the immunoreceptor tyrosine-based activation motif (ITAM) of Fc receptors leading to recruitment of downstream genes necessary for cytoskeletal remodeling suggesting a role for this macrophage subset in Fc receptor-mediated phagocytosis [34]. A recent study performed by Villani et al [14] defines the heterogeneity of intermediate monocyte subset based on single-cell RNA sequencing They identified four monocyte subpopulations namely, Mono 1 (representing mostly the classical monocytes and some intermediate monocytes), Mono 2 (containing a major proportion of non-classical monocytes together with some intermediate monocytes), Mono 3, and Mono 4. Tuberculin skin test (TST) positive individuals express higher CD14+ CD16+ monocyte subset than

Preferred response to LPS

Gene signature derived functions

CONCLUSION