Modulation of human macrophage activity by Ascaris antigens is dependent on macrophage polarization state

Almeida, Sara; Nejsum, Peter; Williams, Andrew R.

doi:10.1016/j.imbio.2017.11.003

Cited by 22 publications

(18 citation statements)

References 27 publications

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“…Both M1-like and M2-like macrophage subsets are involved in parasitic infections; macrophages undergo, in general, a dynamic switch toward the M2-like phenotype at later stages [ 71 ]. Given the putative anti-inflammatory effects of helminth Ascaris suum antigens in mice, studies have been conducted on human cells and showed that such antigens appear to exert stronger activity when acting upon macrophages that have already been polarized to the M1-like phenotype, rather than influencing the polarization process per se [ 72 ]. However, very few studies conducted on human patients or cells have been conducted regarding the in vivo and/or ex vivo effect of parasites on macrophage polarization.…”

Section: Swinging Macrophage Polarization During Infectionsmentioning

confidence: 99%

Role of Human Macrophage Polarization in Inflammation during Infectious Diseases

Atri

Guerfali

Laouini

2018

IJMS

1,034

811

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Experimental models have often been at the origin of immunological paradigms such as the M1/M2 dichotomy following macrophage polarization. However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between M1-like and M2-like macrophages is rather represented by a continuum, where boundaries are still unclear. Indeed, human infectious diseases, are characterized by either a back and forth or often a mixed profile between the pro-inflammatory microenvironment (dominated by interleukin (IL)-1β, IL-6, IL-12, IL-23 and Tumor Necrosis Factor (TNF)-α cytokines) and tissue injury driven by classically activated macrophages (M1-like) and wound healing driven by alternatively activated macrophages (M2-like) in an anti-inflammatory environment (dominated by IL-10, Transforming growth factor (TGF)-β, chemokine ligand (CCL)1, CCL2, CCL17, CCL18, and CCL22). This review brews the complexity of the situation during infectious diseases by stressing on this continuum between M1-like and M2-like extremes. We first discuss the basic biology of macrophage polarization, function, and role in the inflammatory process and its resolution. Secondly, we discuss the relevance of the macrophage polarization continuum during infectious and neglected diseases, and the possibility to interfere with such activation states as a promising therapeutic strategy in the treatment of such diseases.

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Section: Swinging Macrophage Polarization During Infectionsmentioning

confidence: 99%

Role of Human Macrophage Polarization in Inflammation during Infectious Diseases

Atri

Guerfali

Laouini

2018

IJMS

1,034

811

View full text Add to dashboard Cite

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“…Likewise, many other HDPs, such as body fluid from adult Ascaris suum , have also been documented to induce hyporesponsiveness in human APCs treated with LPS and modulate different human macrophage phenotypes ( 43 , 44 ). Although HDPs mainly seem to impair TLR4-associated inflammatory responses, it appears that these components tend to target manifold pathways in TLRs and CLRs signaling.…”

Section: Helminth-derived Products (Hdps) As Potent Immunomodulatorsmentioning

confidence: 99%

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

et al. 2018

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Helminth parasites are masters at manipulating host immune responses, using an array of sophisticated mechanisms. One of the major mechanisms enabling helminths to establish chronic infections is the targeting of pattern recognition receptors (PRRs) including toll-like receptors, C-type lectin receptors, and the inflammasome. Given the critical role of these receptors and their intracellular pathways in regulating innate inflammatory responses, and also directing adaptive immunity toward Th1 and Th2 responses, recognition of the pathways triggered and/or modulated by helminths and their products will provide detailed insights about how helminths are able to establish an immunoregulatory environment. However, helminths also target PRRs-independent mechanisms (and most likely other yet unknown mechanisms and pathways) underpinning the battery of different molecules helminths produce. Herein, the current knowledge on intracellular pathways in antigen presenting cells activated by helminth-derived biomolecules is reviewed. Furthermore, we discuss the importance of helminth-derived vesicles as a less-appreciated components released during infection, their role in activating these host intracellular pathways, and their implication in the development of new therapeutic approaches for inflammatory diseases and the possibility of designing a new generation of vaccines.

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“…In addition, we have recently shown that A. suum body fluid (ABF) has a strong overall immunosuppressive effect on DCs including inhibition of pro‐inflammatory lipopolysaccharide (LPS)‐induced TNF‐α and IL‐6 secretion [13]. Similarly, ABF has a pronounced suppressive effect on the secretion of TNF‐α, IL‐6 and IL‐10 from LPS‐stimulated classically activated human macrophages [14]. The active constituents of the ABF responsible for the suppressive effect on DCs and macrophages have not yet been identified.…”

Section: Introductionmentioning

confidence: 99%

Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite–host cross talk

Hansen

Fromm

Andersen

et al. 2019

J of Extracellular Vesicle

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103

101

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The prevalent porcine helminth, Ascaris suum, compromises pig health and reduces farm productivity worldwide. The closely related human parasite, A. lumbricoides, infects more than 800 million people representing a disease burden of 1.31 million disability-adjusted life years. The infections are often chronic in nature, and the parasites have a profound ability to modulate their hosts' immune responses. This study provides the first in-depth characterisation of extracellular vesicles (EVs) from different developmental stages and body parts of A. suum and proposes the role of these vesicles in the host-parasite interplay. The release of EVs from the third-(L3) and fourth-stage (L4) larvae and adults was demonstrated by transmission electron microscopy (TEM), and sequencing of EV-derived RNA identified a number of microRNAs (miRNAs) and transcripts of potential host immune targets, such as IL-13, IL-25 and IL-33, were identified. Furthermore, proteomics of EVs identified several proteins with immunomodulatory properties and other proteins previously shown to be associated with parasite EVs. Taken together, these results suggest that A. suum EVs and their cargo may play a role in host-parasite interactions. This knowledge may pave the way to novel strategies for helminth infection control and knowledge of their immune modulatory potential.

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Modulation of human macrophage activity by Ascaris antigens is dependent on macrophage polarization state

Cited by 22 publications

References 27 publications

Role of Human Macrophage Polarization in Inflammation during Infectious Diseases

Role of Human Macrophage Polarization in Inflammation during Infectious Diseases

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite–host cross talk

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