The CD14+ CD16+ blood monocytes: their role in infection and inflammation

Ziegler-Heitbrock, Loems

doi:10.1189/jlb.0806510

Cited by 880 publications

(856 citation statements)

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“…Furthermore, our results could be also relevant in other diseases characterized by high CD16 + Mo numbers, such as HIV, rheumatoid arthritis, sepsis, atherosclerosis, Kawasaki disease, and hemolytic uremic syndrome, among others [57]. If CD16 − /CD16 + Mo ratio remains at normal levels, the impact of CD16 + Mos is negligible but under certain pathological conditions -characterized by more than 15% CD16 + Mos -their contribution has a major effect on total DCs population function.…”

Section: Discussionmentioning

confidence: 69%

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

et al. 2013

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Tuberculosis (TB) is one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16 + /CD16 − Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16 − Mos differentiated into CD1a + DC-SIGN high cells achieving an efficient recall response, while CD16 + Mos differentiated into a CD1a − DC-SIGN low population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16 + Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16 − Mo differentiation. Furthermore, depletion of CD16 + Mos indeed improved the differentiation of Mos from TB patients toward CD1a + DC-SIGN high DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16 + Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs. Keywords: Dendritic cells r Monocyte differentiation r Tuberculosis See accompanying Commentary by Lugo-Villarino and NeyrollesAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMonocytes (Mos) are large circulating leukocytes of the myeloid lineage that mediate essential functions of innate immunity including phagocytosis and cytokine production [1,2]. Mos are produced Correspondence: Dr. Luciana Balboa e-mail: luciana_balboa@hotmail.com in the bone marrow and released into the blood, and circulate in blood or reside in a spleen reservoir and, upon tissue infiltration they can differentiate into macrophages (M s) or DCs. Although human blood Mos are a highly heterogeneous population, two main subsets have been described: CD14 + CD16 − "classical" Mos are the major Mo population and CD14 + CD16 + Mos, the minor one (5-10% of total Mos). The latter subset has a more mature phenotype and an enhanced proinflammatory activity [3]. This heterogeneity has led to the hypothesis that Mos are committed to specific functions prior to tissue infiltration [4]. Also, C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 336Luciana Balboa et al. Eur. J. Immunol. 2013. 43: 335-347 an imbalance in the relative proportions of the subsets during acute inflammation [5] and several infectious diseases [6][7][8][9][10] including tuberculosis (TB) [11,12] has been described. TB, a disease that mainly affects the respiratory system, infects onethird of the world's population and kills 2 million people each year [13]. The success o...

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Section: Discussionmentioning

confidence: 69%

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

et al. 2013

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“…At rest, a majority of the CD14 ϩ CD16 ϩ monocytes are not present in the peripheral circulation but reside in the marginal pool and are released into the peripheral circulation via catecholaminemediated sympathetic mechanisms (78). The time course of peripheral blood inflammatory monocyte expansion during disease (Ͼ50%) (25) has been found to follow systemic cytokine appearance (7,91); however, with physical stress, an immediate mobilization of CD14 ϩ CD16 ϩ cells from the marginal pool is observed (31,78). EHS elicited a similar increase in CD14 ϩ CD16 ϩ subsets, with a greater increase observed in TR subjects.…”

Section: Discussionmentioning

confidence: 99%

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Selkirk¹,

McLellan²,

Wright³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Selkirk GA, McLellan TM, Wright HE, Rhind SG. Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals. Am J Physiol Regul Integr Comp Physiol 296: R575-R586, 2009. First published January 21, 2009 doi:10.1152/ajpregu.90683.2008.-This study examined intracellular cytokine, heat shock protein (HSP) 72, and cellular apoptosis in classic and inflammatory CD14 ϩ monocyte subsets during exertional heat stress (EHS). Subjects were divided into endurance-trained [TR; n ϭ 12, peak aerobic power (V O2peak) ϭ 70 Ϯ 2 ml⅐ kg lean body mass (LBM) Ϫ1 ⅐ min Ϫ1 ] and sedentary-untrained (UT; n ϭ 11, V O2peak ϭ 50 Ϯ 1 ml⅐ kg LBM Ϫ1 ⅐ min Ϫ1 ) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber (40°C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5°C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0°C/Exh) were analyzed for cytokines (TNF-␣, IL-1␤, IL-6, IL-1ra, and IL-10) in CD14 ϩϩ CD16 Ϫ /CD14 ϩ CD16 ϩ and HSP72/apoptosis in CD14 Bri / CD14 Dim subsets. In addition, serum levels of extracellular (e)HSP72 were also examined. Baseline and Exh samples were separately stimulated with LPS (1 g/ml) or heat shocked (42°C) and cultured in vitro for 2 h. A greater temperature-dependent increase in CD14 ϩ CD16 ϩ cells was observed in TR compared with UT subjects as well as a greater LPS tolerance following in vitro LPS stimulation. TNF-␣ and IL-1␤ cytokine expression was elevated in CD14 ϩ CD16 ϩ but not in CD14 ϩϩ CD16 Ϫ cells. A greater induction of intracellular HSP72 and eHSP72 was observed in TR compared with UT subjects, which coincided with reduced apoptosis at Exh and following in vitro heat shock. Induced HSP in vitro was not uniform across CD14 ϩ subsets. Findings suggest that circulating CD14 ϩ CD16 ϩ , but not CD14 ϩϩ CD16 Ϫ monocytes, contribute to the proinflammatory cytokine profiles observed during EHS. In addition, the enhanced HSP72 response in endurance-trained individuals may confer improved heat tolerance through both anti-inflammatory and anti-apoptotic mechanisms. immune function; cardiovascular/thermoregulatory strain; flow cytometry; heat shock protein PERIPHERAL BLOOD MONOCYTES play an important role in protection against invading pathogens and activation of innate immunity (46). Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82, 90). The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6, 62, 64, 90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the clas...

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“…Four subtypes have been identified including the CD304 1 (BDCA4) pDCs and the cDCs that include the CD141 1 (BDCA3) and CD1b/c 1 (BDCA1) subsets. 12 A fourth subset that is CD16 1 has been suggested to be a subset of both DC 12 and monocytes, 13 but is now considered to be a monocyte in a recent reclassification of the monocyte and DC subsets in human blood. 14 The CD141 1 DCs have been suggested to be equivalent to the mouse CD8 1 DCs sharing a similar transcriptional signature 15 and expression of Necl2, CLEC9A and XCR1.…”

Section: Introductionmentioning

confidence: 99%

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34+ stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin

et al. 2012

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Dendritic cells (DCs) are immune cells specialized to capture, process and present antigen to T cells in order to initiate an appropriate adaptive immune response. The study of mouse DC has revealed a heterogeneous population of cells that differ in their development, surface phenotype and function. The study of human blood and spleen has shown the presence of two subsets of conventional DC including the CD1b/c 1 and CD141 1 CLEC9A 1 conventional DC (cDC) and a plasmacytoid DC (pDC) that is CD304 1 CD123 1 . Studies on these subpopulations have revealed phenotypic and functional differences that are similar to those described in the mouse. In this study, the three DC subsets have been generated in vitro from human CD34 1 precursors in the presence of fms-like tyrosine kinase 3 ligand (Flt3L) and thrombopoietin (TPO). The DC subsets so generated, including the CD1b/c 1 and CLEC9A 1 cDCs and CD123 1 pDCs, were largely similar to their blood and spleen counterparts with respect to surface phenotype, toll-like receptor and transcription factor expression, capacity to stimulate T cells, cytokine secretion and cross-presentation of antigens. This system may be utilized to study aspects of DC development and function not possible in vivo.

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The CD14+ CD16+ blood monocytes: their role in infection and inflammation

Cited by 880 publications

References 116 publications

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34+ stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin

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