<i>Nippostrongylus brasiliensis</i> infection leads to the development of emphysema associated with the induction of alternatively activated macrophages

Marsland, Benjamin J.; Kurrer, Michael; Reissmann, Regina; Harris, Nicola L.; Köpf, Manfred

doi:10.1002/eji.200737827

Cited by 100 publications

(134 citation statements)

References 27 publications

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“…1) [43], suggesting they are an enduring element of the post-Nb lung. It is not clear if the granular phenotype is maintained as a consequence of longlived cells, or it represents scavenging of granules released after cell death.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of lung macrophage activation in response to helminth infection

Siracusa

Reece

Urban

et al. 2008

Journal of Leukocyte Biology

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Most of our understanding of the development and phenotype of alternatively activated macrophages (AAMs) has been obtained from studies investigating the response of bone marrow-and peritoneal-derived cells to IL-4 or IL-13 stimulation. Comparatively little is known about the development of AAMs in the lungs, and how the complex signals associated with pulmonary inflammation influence the AAM phenotype. Here, we use Nippostrongylus brasiliensis to initiate AAM development and define the dynamics of surface molecules, gene expression, and cell function of macrophages isolated from lung tissue at different times postinfection (PI). Initially, lung macrophages take on a foamy phenotype, up-regulate MHC and costimulatory molecules, express reduced levels of TNF and IL-12, and undergo proliferation. Cells isolated between days 8 and 15 PI adopt a dense, granular phenotype and exhibit reduced levels of costimulatory molecules and elevated levels of programmed death ligand-1 (PDL-1) and PDL-2 and an increase in IL-10 expression. Functionally, AAMs isolated on days 13-15 PI demonstrate an enhanced capacity to take up and sequester antigen. However, these same cells did not mediate antigen-specific T cell proliferation and dampened the proliferation of CD3/CD28-activated CD4 ؉ T cells. These data indicate that the alternative activation of macrophages in the lungs, although initiated by IL-4/IL-13, is a dynamic process that is likely to be influenced by other immune and nonimmune factors in the pulmonary environment. J.

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Section: Discussionmentioning

confidence: 99%

Dynamics of lung macrophage activation in response to helminth infection

Siracusa

Reece

Urban

et al. 2008

Journal of Leukocyte Biology

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“…In vivo counterparts of M2 macrophage polarization have been observed in tissue remodelling during ontogenesis [28], chronic inflammation [29][30][31][32][33][34][35][36][37][38][39][40][41][42], cancer [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 immunopathology [35][36][37][38][39][40][41][50][51][52].…”

Section: Activation and Adaptive Responses Of Macrophagesmentioning

confidence: 99%

“…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 immunopathology [35][36][37][38][39][40][41][50][51][52].…”

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confidence: 99%

From phagocyte diversity and activation to probiotics: Back to Metchnikoff

Mantovani

2008

Eur J Immunol

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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...

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“…In a primary infection, the host immune response to these events appears too slow to affect worm survival or fecundity. However, from 4 days after primary infection, enhanced anamnestic immune responses begin to develop that reduce the viability of worms and significantly reduce the lung haemorraging 10 . While several cell types have been described as participating in the repair mechanisms following Nb infection, their role in anamnestic immunity remains largely undefined.…”

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confidence: 99%

ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms

et al. 2015

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Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4 þ T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4 þ T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2's role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4 þ T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.

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Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages

Cited by 100 publications

References 27 publications

Dynamics of lung macrophage activation in response to helminth infection

Dynamics of lung macrophage activation in response to helminth infection

From phagocyte diversity and activation to probiotics: Back to Metchnikoff

ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms

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