From phagocyte diversity and activation to probiotics: Back to Metchnikoff

Abstract

In this issue of the European Journal of Immunology, Siamon Gordon gives a detailed account of Metchnikoff's life and his achievements (Eur. J. Immunol. 2008. 38: 3257-3264). Looking back at the roots of innate immunity stimulates reflections on open issues in the field. Here, I give a personal view of some of these issues, including myeloid-derived suppressor cells, macrophage polarization and adaptive responses of mononuclear phagocytes. Key words: Macrophage activation Á Macrophages Á M1/M2 polarization Á Probiotics See accompanying article by Gordon IntroductionIn his scholarly review [1], Siamon Gordon tracks the roots of innate immunity to Elie Metchnikoff. The essay provides a fascinating insight into Metchnikoff's scientific life and how he tackled fundamental issues in science, some of which remain with us to this day. The perspective offered by a major player in the very same field of phagocytes and innate immunity [2,3] adds flavour and fascination to this article not necessarily present in other accounts [4]. Such a reflection on a central part of modern immunology stimulates consideration of remaining open issues and there follows a personal view of some of these.Phagocyte heterogeneity: From microphage-macrophage dichotomy to myeloid-derived suppressor cellsThe fundamental distinction between polymorphonuclear leukocytes (microphages) and mononuclear phagocytes (macrophages) was a major first step in the dissection of phagocyte heterogeneity and lineage differentiation. The identification of myeloid-derived suppressor cells (MDSC) [5][6][7] raises the questions whether the classic sharp distinction between the myeloid and the monocyte-macrophage differentiation and activation pathways is appropriate. In contrast to long-held views, neutrophils express specific transcriptional programmes in response to environmental signals [8]. MDSC include immature myeloid precursors that can further differentiate, and play a key role in the suppression of adaptive immunity in diverse pathological conditions ranging from cancer to chronic infections [5][6][7]. Are we dealing with a blurring of a classic distinction or with a well-defined third phagocyte population? Using current identification and separation criteria (e.g. Gr1, CD11b, F4/80) MDSC in the blood and lymphoid organs are a mixed population, which includes myeloid cells at different stages of differentiation and mononuclear phagocytes. Thus, the definition of MDSC remains an operational one rather than that of a cell type, a reality that is frequently neglected. The issue of lineage of the actual effectors of MDSC-mediated suppression is even more relevant when their recruitment and activation in non-lymphoid tissues is considered. For instance, do MDSC retain an immature phenotype in tumour tissues or do they differentiate into tumourassociated macrophages [9][10][11] [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of i...

Probiotic Properties of the 2-Substituted (1,3)-β- d -Glucan-Producing Bacterium Pediococcus parvulus 2.6

“…If the latter explanation is true, then EPS could be considered a bona fide beneficial immunomodulator. In summary, the comparative analysis of ␤-glucan-producing and nonproducing strains performed in this work has provided insights into the debated issues of probiotic properties of EPSproducing LAB (3) and the role of EPS in the immunomodulation of macrophages (20).…”

Macrophage Diversity and Polarization in Atherosclerosis

“…24 In vivo counterparts of M2 macrophage polarization have been observed in tissue remodeling during ontogeny, 29 in placenta, 30 and in various pathological conditions. 20,31 The M1/M2 macrophage polarization paradigm should be viewed in the light of the plasticity and flexibility of mononuclear phagocytes mirroring the Th1/ Th2 paradigm and their activating products (IFN␥ and IL-4). 20 Indeed, different signals give rise to a complex multidimensional variety of macrophage activation profiles.…”

“…20,31 The M1/M2 macrophage polarization paradigm should be viewed in the light of the plasticity and flexibility of mononuclear phagocytes mirroring the Th1/ Th2 paradigm and their activating products (IFN␥ and IL-4). 20 Indeed, different signals give rise to a complex multidimensional variety of macrophage activation profiles. 3,22 The relation between monocyte subsets and macrophage polarization remains unclear.…”

Toxoplasma gondii GRA15II effector-induced M1 cells ameliorate liver fibrosis in mice infected with Schistosomiasis japonica

“…4,8,47 Classically activated macrophages (M1 cells) mediate resistance to intracellular pathogens through the expression of cytokines and chemokines such as IL-12, CXCL9 and CXCL10, which promote the Th1 dominant response. [48][49][50] In contrast, alternatively activated macrophages (M2 cells) are critically involved in granuloma formation and fibrosis via the Th2 cytokine response. 19,43,[51][52][53][54] Recent studies revealed that the polymorphic dense granule protein GRA15 II and rhoptry protein ROP16 I/III secreted by type II or type I/III Toxoplasma induced differential macrophage polarization.…”