Trends in Parasitology
Volume 28, Issue 10, October 2012, Pages 408-416
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Review
The diverse roles of monocytes in inflammation caused by protozoan parasitic diseases

https://doi.org/10.1016/j.pt.2012.07.008Get rights and content

The mononuclear phagocyte system (MPS), comprising monocytes, macrophages, and dendritic cells (DCs), plays an important role in the control of disease, but can also contribute to the establishment of persistent infections. Monocytes are derived from progenitors in the bone marrow. Once in circulation, they migrate into the tissues, differentiate into macrophages, and phagocytose microbes under inflammatory conditions. However, recent work shows they not only act as phagocytes, but are also precursors for particular types of DCs, inflammatory macrophages, and tissue macrophages. The role of monocytes during inflammation in models of bacterial and viral infections, cancer, atherosclerosis, and autoimmunity has been widely studied and reported. In this review we focus on the less understood role of monocytes in protozoan infections.

Section snippets

Monocytes and their reservoir

Monocytes, along with other granulocytes, including neutrophils, basophils, eosinophils, mast cells, and natural killer (NK) cells, are part of the innate immune system. They are the first line of defense of the body against pathogen challenge. Monocytes are mononuclear leukocytes that contain a bean-shaped nucleus. They express CD11b, CD14, and CD11c in humans, and CD11b and F4/80 in mice [1], but lack other lineage markers for T cells, NK cells, B cells, and DCs. Monocytes originate from a

Plasticity of monocytes

The multipotent potential of monocytes is determined by the inflammatory environment prevalent in the host during infection and disease. The trafficking of monocytes and recruitment into different tissues has been previously reviewed 10, 11. Extensive work has also been performed to map the fate of MDPs and monocytes [3]. Monocytes themselves can be phagocytic and/or present antigen to T cells 4, 7, 12. Different subsets of inflammatory DCs, such as monocyte-derived DCs [13], tumor necrosis

Protozoan parasitic diseases and the mononuclear phagocyte system

Traditionally, monocytes, macrophages, and DCs were thought to play similar roles during protozoan infections. Blood monocytes and tissue macrophages were known to be phagocytic and kill parasites via oxidative and non-oxidative mechanisms. In addition, tissue macrophages could serve as hosts for long-term replication and survival of particular protozoan parasites, protecting them from the host extracellular environment. The role of DCs was assumed to be mainly antigen presentation to T cells.

Monocyte subsets

Monocytes are a heterogeneous population of cells with varied functions, making their characterization and phenotyping difficult. Almost two decades ago, human peripheral blood monocytes were distinguished based on the expression of CD14 and CD16. Broadly, human blood monocytes are divided into two major subsets (CD14hi/++ CD16, and CD14dim CD16+ monocytes) and a minor subset (CD14+ CD16+ CD64+ monocytes) 21, 22, 23. The former major monocytes subset, referred to as CD14+ monocytes are ∼18 μm

Inflammatory monocytes in protozoan parasitic diseases

The role of inflammatory monocytes has been well described in models with L. monocytogenes and fungal infections, but relatively little is known about their role in protozoan parasitic models, although some studies have been reported in infections caused by Leishmania spp., Plasmodium spp., Toxoplasma gondii and Trypanosoma brucei (Table 2). Inflammatory monocytes, characterized by the expression of CD11b+ Ly6Chi, require the chemokine receptor CCR2 for extravasion from the bone marrow into

Studying monocytes in protozoan parasitic diseases

The past 10 years has seen great advances in our knowledge of the MPS. The identification of two main monocyte subsets, the development of enrichment and adoptive transfer techniques for monocytes, and the generation of CX3CR1GFP/+ mice have been crucial for dissecting the role of monocytes in protozoan parasitic diseases 1, 44. The difficulty in isolating murine monocytes due to their relative rarity, heterogeneity, and their inability to proliferate, often limits their study. Examination of

Patrolling monocytes in protozoan parasitic diseases

The role of patrolling monocytes (CD11b+ Ly6Clo CCR2 CX3CR1+) during protozoan parasitic infections has not been extensively investigated. This could partly be explained by their resident status in non-inflammatory tissue sites and blood vessels, rather than being recruited to sites of infection and/or inflammation. Patrolling monocytes (Box 2) have been implicated in wound healing and autoimmune diseases [17]. Many protozoan parasites, including Plasmodium spp., Leishmania spp., T. brucei,

The role of the mononuclear phagocyte system in human protozoan parasitic diseases

Diseases caused by protozoan parasites, including leishmaniasis, malaria, Chagas disease, and African trypanosomiasis, are endemic in regions of poor socioeconomic status, and are often complicated due to coinfection with HIV, tuberculosis, and helminths. These factors, along with the limited access to patient samples, contribute to our limited knowledge on the role of the cells belonging to the MPS and their involvement in protozoan infections.

Drug treatment of patients with post kala-azar

Immune modulation and therapeutic potential of monocytes

The identification of classical/inflammatory monocytes and the non-classical/patrolling monocytes has helped to identify the therapeutic potential of these cells for immune modulation during inflammation. The importance of CCR2 on the former population has been confirmed not only in parasitic diseases, but also in disease caused by bacterial, viral, and fungal infections, as well as cancer and diseases of the nervous system, including multiple sclerosis (MS) and Alzheimer's disease. Patrolling

Concluding remarks

The past decade has seen a rapid increase in our knowledge of monocytes and their roles in disease. Although studies with protozoan parasites have lagged behind those involving other pathogens, cancer, or autoimmune disease, the gap is being rapidly closed. The development of new tools to distinguish monocyte subsets in humans and mice will help to distinguish their roles during protozoan parasite infection and also characterize any relation between subsets during disease. A particularly

Acknowledgments

We thank Madeleine Flynn for assistance with the production of figures. Work from the laboratory of the authors is supported by funding from the Australian National Health and Medical Research Council (NHMRC) and the Australian Government Australia–India Strategic Research Fund.

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