Human Monocyte Subsets at Homeostasis and Their Perturbation in Numbers and Function in Filarial Infection

Semnani, Roshanak Tolouei; Moore, Vanessa; Bennuru, Sasisekhar; McDonald-Fleming, Renee; Ganesan, Sundar; Cotton, Rachel N.; Ray, Anuradha; Babu, Subash; Nutman, Thomas B.

doi:10.1128/iai.01973-14

Cited by 28 publications

(14 citation statements)

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“…Non-classical monocytes did not show a detectable response to IL-4. This result is consistent with other studies, which found that non-classical monocytes have a reduced cytokine response to IL-4 [ 23 ]. Differences between CD16+ and CD16- monocytes in induction of some cell markers during dendritic cell differentiation by GM-CSF, IL-4 and TNFα have also been reported [ 36 ].…”

Section: Discussionsupporting

confidence: 94%

“…Higher levels of binding of the 14–23 antibody were observed on classical monocytes, raising the possibility that other peptides in addition to CLIP may generate the conformation recognized by mAb 14–23, although this antibody was generated by immunization of HLA-DR3 transgenic mice with HLA-DR3/CLIP complexes [ 17 ]. Interestingly, the classical monocyte has been observed to be the most efficient at inducing autologous T cell proliferation, although by a small degree [ 21 , 23 ]. These results suggest that although the intermediate subset has the highest level of MHCII, the lowest CLIP:MHCII ratio, and high levels of costimulatory molecules [ 7 ], the classical subset may present relevant self-peptides for homeostatic proliferation [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines

et al. 2017

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Monocytes play a critical role in the innate and adaptive immune systems, performing phagocytosis, presenting antigen, and producing cytokines. They are a heterogeneous population that has been divided in humans into classical, intermediate, and non-classical subsets, but the roles of these subsets are incompletely understood. In this study, we investigated the expression patterns of MHC class II (MHCII) and associated molecules and find that the intermediate monocytes express the highest levels of the MHC molecules, HLA-DR (tested in n = 30 samples), HLA-DP (n = 30), and HLA-DQ (n = 10). HLA-DM (n = 30), which catalyzes the peptide exchange on the MHC molecules, is also expressed at the highest levels in intermediate monocytes. To measure HLA-DM function, we measured levels of MHCII-bound CLIP (class II invariant chain peptide, n = 23), which is exchanged for other peptides by HLA-DM. We calculated CLIP:MHCII ratios to normalize CLIP levels to MHCII levels, and found that intermediate monocytes have the lowest CLIP:MHCII ratio. We isolated the different monocyte subsets (in a total of 7 samples) and analyzed their responses to selected cytokines as model of monocyte activation: two M1-polarizing cytokines (IFNγ, GM-CSF), an M2-polarizing cytokine (IL-4) and IL-10. Classical monocytes exhibit the largest increases in class II pathway expression in response to stimulatory cytokines (IFNγ, GM-CSF, IL-4). All three subsets decrease HLA-DR levels after IL-10 exposure. Our findings argue that intermediate monocytes are the most efficient constitutive antigen presenting subset, that classical monocytes are recruited into an antigen presentation role during inflammatory responses and that IL-10 negatively regulates this function across all subsets.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines

et al. 2017

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“…The heterogeneity of function and plasticity of monocytes have been described in parasitic infections [48–50] and clearly demonstrated the differential polarization of these cells as described for macrophages. In our study, phenotypic and molecular parameters were evaluated in circulating monocytes from hookworm-infected individuals to investigate the profile of activation and polarization of these cells.…”

Section: Discussionmentioning

confidence: 79%

Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection

et al. 2017

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BackgroundWhile the macrophage polarization is well characterized in helminth infections, the natural heterogeneity of monocytes with multiple cell phenotypes might influence the outcome of neglected diseases, such hookworm infection. Here, we report the profile of monocytes in human hookworm infections as a model to study the regulatory subpopulation of monocytes in helminth infections.MethodsBlood samples were collected from 19 Necator americanus-infected individuals and 13 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were isolated, and immunophenotyping was conducted by flow cytometry. The expressions of genes encoding human nitric oxide synthase (iNOS), interleukin 4 (IL-4), arginase-1 (Arg-1) and glyceraldehyde 3-phosphate dehydrogenase were quantified by qPCR. Plasma levels of IL-4 were determined by sandwich ELISA. Unpaired t-tests or Mann-Whitney tests were used depending on the data distribution.ResultsHookworm infected individuals (HWI) showed a significant increase in the number of monocytes/mm3 (555.2 ± 191.0) compared to that of the non-infected (NI) individuals (120.4 ± 44.7) (p < 0.0001). While the frequencies of CD14+IL-10+ and CD14+IL-12+ cells were significantly reduced in the HWI compared to NI group (p = 0.0289 and p < 0.0001, respectively), the ratio between IL-10/IL-12 producing monocytes was significantly elevated in HWI (p = 0.0004), indicating the potential regulatory activity of these cells. Measurement of IL-4 levels and gene expression of IL-4 and Arg-1 (highly expressed in alternatively activated macrophages) revealed no significant differences between the NI and HWI groups. Interestingly, individuals from the HWI group had higher expression of the iNOS gene (associated with a regulatory profile) (20.27 ± 2.97) compared to the NI group (11.28 ± 1.18, p = 0.0409). Finally, individuals from the HWI group had a significantly higher frequency of CD206+CD23+IL-10+ (7.57 ± 1.96) cells compared to individuals from the NI group (0.35 ± 0.09) (p < 0.001), suggesting that activated monocytes are a potential source of regulatory cytokines during hookworm infection.ConclusionsNatural hookworm infection induces a high frequency of circulating monocytes that present a regulatory profile and promote the downmodulation of the proinflammatory response, which may contribute to prolonged survival of the parasite in the host.

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“…It is worth mentioning that the increase in the percentage of monocytes expressing CD16 was also observed in other pathological conditions, e.g. during bacterial, viral or parasitic infections [20] and in acute or chronic conditions such as sepsis or atherosclerosis [8], chronic liver disease [21], rheumatoid arthritis [22], and renal diseases [23,24].…”

Section: Discussionmentioning

confidence: 83%

Expression of CD163 and HLA-DR molecules on the monocytes in chronic lymphocytic leukemia patients

Kowalska

2020

Folia Histochem Cytobiol.

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Introduction. Human peripheral blood monocytes are the part of the leukemia microenvironment. We examined three monocyte subgroups: classical (CD14 ++ CD16 -), intermediate (CD14 ++ CD16 + ) and non-classical (CD14 + CD16 ++ ) monocytes. As these subpopulations can be also characterized by different levels of HLA-DR and CD163, we evaluated their expression on monocyte subpopulations of patients with chronic lymphocytic leukemia (CLL) and healthy individuals. Material and methods. The monocyte subsets in peripheral blood of CLL patients (n = 40) and healthy controls (n = 10) were evaluated by flow cytometry. The monoclonal antibodies: anti-CD14 FITC, anti-CD16 PE-Cy5, anti-CD163 PE, anti-HLA-DR PE were used. Results. The percentage of CD16-positive monocytes was significantly higher in CLL patients than in healthy donors. The highest percentage of CD163 + monocytes is in the 'classical' (CD14 ++ CD16 -) population. In turn, the non-classical monocytes constituted the majority of cells lacking HLA-DR expression. In CLL patients, there was no statistically significant relationship between the percentage of each monocyte subpopulation and the stage according to Rai Staging of CLL. Conclusions. The presence of CD163 on classical monocytes suggests that these cells have anti-inflammatory properties. Besides, the low expression of HLA-DR on non-classical monocytes may result in impaired ability to stimulate the immune system.

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Human Monocyte Subsets at Homeostasis and Their Perturbation in Numbers and Function in Filarial Infection

Cited by 28 publications

References 28 publications

The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines

The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines

Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection

Expression of CD163 and HLA-DR molecules on the monocytes in chronic lymphocytic leukemia patients

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