Characterization of human peritoneal monocyte/macrophage subsets in homeostasis: Phenotype, GATA6, phagocytic/oxidative activities and cytokines expression

Antonio José Ruiz-Alcaraz,María Luisa Sánchez-Ferrer,María Martínez-Esparza,Pilar García-Peñarrubia,María Tristán-Manzano,Violeta Carmona-Martínez,Francisco Machado-Linde

doi:10.1038/s41598-018-30787-x

Antonio José Ruiz-Alcaraz, María Luisa Sánchez-Ferrer + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-30787-x

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Abstract

Peritoneal macrophages play a critical role in the control of infectious and inflammatory diseases. Although recent progress on murine peritoneal macrophages has revealed multiple aspects on their origin and mechanisms involved in their maintenance in this compartment, little is known on the characteristics of human peritoneal macrophages in homeostasis. Here, we have studied by flow cytometry several features of human peritoneal macrophages obtained from the peritoneal cavity of healthy women. Three peritoneal monocyte/macrophage subsets were established on the basis of CD14/CD16 expression (CD14++CD16−, CD14++CD16+ and CD14highCD16high), and analysis of CD11b, CD11c, CD40, CD62L, CD64, CD80, CD86, CD116, CD119, CD206, HLA-DR and Slan was carried out in each subpopulation. Intracellular expression of GATA6 and cytokines (pro-inflammatory IL-6 and TNF-α, anti-inflammatory IL-10) as well as their phagocytic/oxidative activities were also analyzed, in an attempt to identify genuine resident peritoneal macrophages. Results showed that human peritoneal macrophages are heterogeneous regarding their phenotype, cell complexity and functional abilities. A direct relationship of CD14/CD16 expression, intracellular content of GATA6, and activation/maturation markers like CD206 and HLA-DR, support that the CD14highCD16high subset represents the mature phenotype of steady-state human resident peritoneal macrophages. Furthermore, increased expression of CD14/CD16 is also related to the phagocytic activity.

Highlights

Macrophages are a versatile and heterogeneous cell population that interconnects innate and adaptive immunity and plays a crucial role in many inflammatory diseases, tissue remodelling and wound healing, among others
We have recently identified a new subset of monocyte/macrophages from ascites of cirrhotic patients displaying high expression of CD14 and CD16 referred to as CD14highCD16high, bigger size and more complexity than CD16−/low cells, which is not detected in peripheral blood monocytes[17]
It seems necessary to assess whether the local tissue mediators and macrophage transcription factors that have been identified in mice play equal roles in the biology and development of humans tissue-resident macrophages

Summary

Introduction

Macrophages are a versatile and heterogeneous cell population that interconnects innate and adaptive immunity and plays a crucial role in many inflammatory diseases, tissue remodelling and wound healing, among others These cells reside in all tissues in homeostasis, and are rapidly recruited and differentiated from circulating blood monocytes in response to local danger signals provided by inflammation or microbial invasion[1,2]. Healthy range in acute[11] and chronic[12,13,14,15] inflammatory pathologies These cells produce in vitro TNF-α, IL-6, MIP1α and MIP1β pro-inflammatory cytokines in response to LPS7,14,16 and they are probably expanded from the classical to the intermediate subset and from this to the non-classical subpopulation[10]. Among them a similar set of pro-inflammatory M1 and anti-inflammatory M2 polarization markers was observed, which is compatible with a basal pre-activated state to rapidly respond against any challenge to maintain peritoneal homeostasis

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