Effect of helminth-induced immunity on infections with microbial pathogens
TL;DR: This Review critically assesses whether helminths adversely influence host control of these diseases—AIDS, tuberculosis and malaria—and discusses emerging concepts for how M2 macrophages and helminth-modulated dendritic cells can potentially influence the protective immune response to concurrent infections.
Abstract: Helminth infections are ubiquitous worldwide and can trigger potent immune responses that differ from and potentially antagonize host protective responses to microbial pathogens. In this Review we focus on the three main killers in infectious disease-AIDS, tuberculosis and malaria-and critically assesses whether helminths adversely influence host control of these diseases. We also discuss emerging concepts for how M2 macrophages and helminth-modulated dendritic cells can potentially influence the protective immune response to concurrent infections. Finally, we present evidence advocating for more efforts to determine how and to what extent helminths interfere with the successful control of specific concurrent coinfections.
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TL;DR: The panoply of immunomodulatory mechanisms used by helminths, their potential utility in human disease, and prospective areas of future research are summarized.
Abstract: Helminth parasite infections are associated with a battery of immunomodulatory mechanisms that affect all facets of the host immune response to ensure their persistence within the host. This broad-spectrum modulation of host immunity has intended and unintended consequences, both advantageous and disadvantageous. Thus the host can benefit from suppression of collateral damage during parasite infection and from reduced allergic, autoimmune, and inflammatory reactions. However, helminth infection can also be detrimental in reducing vaccine responses, increasing susceptibility to coinfection and potentially reducing tumor immunosurveillance. In this review we will summarize the panoply of immunomodulatory mechanisms used by helminths, their potential utility in human disease, and prospective areas of future research.
370 citations
Cites background from "Effect of helminth-induced immunity..."
...In addition, helminths can undermine host defenses against other major pathogens, such as Mycobacterium tuberculosis.(3,21) In the case of malaria, however, the consequences of helminth infection are more nuanced, with evidence of increased susceptibility combined with moderated inflammatory responses and hence attenuated disease severity....
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TL;DR: Differentially activated neutrophils in the context of a type 2 immune response therefore prime a long-lived effector macrophage phenotype that directly mediates rapid nematode damage and clearance.
Abstract: We examined the role of innate cells in acquired resistance to the natural murine parasitic nematode, Nippostrongylus brasiliensis. Macrophages obtained from lungs as late as 45 d after N. brasiliensis inoculation were able to transfer accelerated parasite clearance to naive recipients. Primed macrophages adhered to larvae in vitro and triggered increased mortality of parasites. Neutrophil depletion in primed mice abrogated the protective effects of transferred macrophages and inhibited their in vitro binding to larvae. Neutrophils in parasite-infected mice showed a distinct transcriptional profile and promoted alternatively activated M2 macrophage polarization through secretory factors including IL-13. Differentially activated neutrophils in the context of a type 2 immune response therefore prime a long-lived effector macrophage phenotype that directly mediates rapid nematode damage and clearance.
267 citations
TL;DR: Data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, which could partially restore antiviral immunity.
Abstract: The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this in the context of virus-helminth coinfection. Helminth coinfection resulted in impaired antiviral immunity and was associated with changes in the microbiota and STAT6-dependent helminth-induced alternative activation of macrophages. Notably, helminth-induced impairment of antiviral immunity was evident in germ-free mice, but neutralization of Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, could partially restore antiviral immunity. These data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1.
234 citations
TL;DR: It is reported that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity, and persistent disruption of communication between tissues and the immune system following clearance of an acute infection represents an inflection point beyond which tissue homeostasis and immunity is compromised for the long- term.
225 citations
Cites background from "Effect of helminth-induced immunity..."
...What remains unclear is whether acute infections produce persistent changes that negatively impact immune function, and if so, what are the mechanisms of such effects? These questions are especially compelling in light of the rising incidence of inflammatory disorders, particularly involving those diseases affecting barrier tissues such as inflammatory bowel disease, psoriasis, allergy, and asthma (Molodecky et al., 2012; Salgame et al., 2013)....
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...These questions are especially compelling in light of the rising incidence of inflammatory disorders, particularly involving those diseases affecting barrier tissues such as inflammatory bowel disease, psoriasis, allergy, and asthma (Molodecky et al., 2012; Salgame et al., 2013)....
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...Chronic infections in particular can have significant bystander consequences on the capacity of the host to respond to subsequent challenges (Barton et al., 2007; Cadwell et al., 2010; Jamieson et al., 2013; Osborne et al., 2014; Salgame et al., 2013)....
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TL;DR: The homeostatic role of ILC2s in setting the activation threshold in the lung and underline their implications in anti-bacterial defenses are highlighted.
182 citations
Cites background from "Effect of helminth-induced immunity..."
...While type 2 responses, as seen upon helminth infections, are known to impair defenses against mycobacteria (Monin et al., 2015; Salgame et al., 2013), we now report that even homeostatic type 2 conditions impact on lung immunity, illustrated by reduced lung inflammation upon LPS challenge and a…...
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...While type 2 responses, as seen upon helminth infections, are known to impair defenses against mycobacteria (Monin et al., 2015; Salgame et al., 2013), we now report that even homeostatic type 2 conditions impact on lung immunity, illustrated by...
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References
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TL;DR: This Review suggests a new grouping of macrophages based on three different homeostatic activities — host defence, wound healing and immune regulation, and proposes that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation.
Abstract: Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
7,384 citations
TL;DR: The four stages of orderly inflammation mediated by macrophages are discussed: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis.
Abstract: Macrophages are strategically located throughout the body tissues, where they ingest and process foreign materials, dead cells and debris and recruit additional macrophages in response to inflammatory signals They are highly heterogeneous cells that can rapidly change their function in response to local microenvironmental signals In this Review, we discuss the four stages of orderly inflammation mediated by macrophages: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis We also discuss the protective and pathogenic functions of the various macrophage subsets in antimicrobial defence, antitumour immune responses, metabolism and obesity, allergy and asthma, tumorigenesis, autoimmunity, atherosclerosis, fibrosis and wound healing Finally, we briefly discuss the characterization of macrophage heterogeneity in humans
4,182 citations
TL;DR: The cellular sources of these cytokines, receptor signaling pathways, and induced markers and gene signatures are reviewed and the concept of macrophage activation in the context of the immune response is revisit.
Abstract: Macrophages are innate immune cells with well-established roles in the primary response to pathogens, but also in tissue homeostasis, coordination of the adaptive immune response, inflammation, resolution, and repair. These cells recognize danger signals through receptors capable of inducing specialized activation programs. The classically known macrophage activation is induced by IFN-gamma, which triggers a harsh proinflammatory response that is required to kill intracellular pathogens. Macrophages also undergo alternative activation by IL-4 and IL-13, which trigger a different phenotype that is important for the immune response to parasites. Here we review the cellular sources of these cytokines, receptor signaling pathways, and induced markers and gene signatures. We draw attention to discrepancies found between mouse and human models of alternative activation. The evidence for in vivo alternative activation of macrophages is also analyzed, with nematode infection as prototypic disease. Finally, we revisit the concept of macrophage activation in the context of the immune response.
2,515 citations
TL;DR: The authors would like to include as an addendum the contribution of R. Stout and J. Suttles to the conceptual framework of macrophage plasticity that was mentioned in the Review.
Abstract: Nature Reviews Immunology 8, 958–969 (2008) The authors would like to include as an addendum the contribution of R. Stout and J. Suttles to the conceptual framework of macrophage plasticity that was mentioned in our Review. Their ideas on the ability of macrophages to change their functional phenotype in response to their tissue environment were previously published in two review articles (J.
1,523 citations
TL;DR: It is revealed that a distinct process exists in which tissue macrophages undergo rapid in situ proliferation in order to increase population density, and expansion of innate cells necessary for pathogen control or wound repair can occur without recruitment of potentially tissue-destructive inflammatory cells.
Abstract: A defining feature of inflammation is the accumulation of innate immune cells in the tissue that are thought to be recruited from the blood. We reveal that a distinct process exists in which tissue macrophages undergo rapid in situ proliferation in order to increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under the control of the archetypal T(H)2 cytokine interleukin-4 (IL-4) and was a fundamental component of T(H)2 inflammation because exogenous IL-4 was sufficient to drive accumulation of tissue macrophages through self-renewal. Thus, expansion of innate cells necessary for pathogen control or wound repair can occur without recruitment of potentially tissue-destructive inflammatory cells.
1,270 citations