The phenotype and function of naturally existing regulatory dendritic cells in nematode-infected mice

Li, Zhaotao; Liu, Guiyun; Chen, Yue; Liu, Yunfeng; Liu, Boyu; Su, Zhendong

doi:10.1016/j.ijpara.2011.06.008

Cited by 22 publications

(20 citation statements)

References 34 publications

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“…In the first instance, the question should be addressed of which host cells are targeted by HES. Previous work on H. polygyrus infection has highlighted the parasite's suppressive effects through dendritic cells [74][75][76] an equivalent amount of recombinant mammalian TGF-β could not suppress allergic immune responses at sensitisation or at challenge; HES suppression at sensitisation was heat-stable, while the HES TGF-β signal is heat labile [54]; and Treg proportions, numbers and activation levels were lower with HES administration at sensitisation than in positive controls. Therefore, we hypothesise that HES contains other immunomodulatory factors than the TGF-β mimic and these are largely responsible for the suppressive effect seen with HES administration at sensitisation.…”

Section: Discussionmentioning

confidence: 99%

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus

McSorley

O'Gorman

Blair³

et al. 2012

Eur J Immunol

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Allergic asthma is less prevalent in countries with parasitic helminth infections, and mice infected with parasites such as Heligmosomoides polygyrus are protected from allergic airway inflammation. To establish whether suppression of allergy could be mediated by soluble products of this helminth, we tested H. polygyrus excretory-secretory (HES) material for its ability to impair allergic inflammation. When HES was added to sensitising doses of ovalbumin, the subsequent allergic airway response was suppressed, with ablated cell infiltration, a lower ratio of effector (CD4 + CD25 + Foxp3 − ) to regulatory (CD4 + Foxp3 + ) T (Treg) cells, and reduced Th1, Th2 and Th17 cytokine production. HES exposure reduced IL-5 responses and eosinophilia, abolished IgE production and inhibited the type 2 innate molecules arginase-1 and RELM-α (resistin-like molecule-α). Although HES contains a TGF-β-like activity, similar effects in modulating allergy were not observed when administering mammalian TGF-β alone. HES also protected previously sensitised mice, suppressing recruitment of eosinophils to the airways when given at challenge, but no change in Th or Treg cell populations was apparent. Because heat-treatment of HES did not impair suppression at sensitisation, but compromised its ability to suppress at challenge, we propose that HES contains distinct heat-stable and heat-labile immunomodulatory molecules, which modulate pro-allergic adaptive and innate cell populations.Keywords: Allergy r Eosinophils r IgE r Infection r Macrophages IntroductionAllergic asthma has dramatically increased in prevalence in developing countries, exceeding 5% of the Western European and North American populations [1]. This contrasts with much lower asthma incidence in tropical countries that have significant levels of parasite infections, and these observations have stimulated research into the effects of parasitic organisms on human allergy [2][3][4]. From these studies, it has emerged that allergic diseases are least common in parts of the world with high helminth endemicity, and that within endemic populations the prevalence of atopy is significantly lower in individuals with chronic worm infections [5][6][7][8][9][10].Correspondence: Dr. Rick M. Maizels e-mail: rick.maizels@ed.ac.ukWhile a causal link between human helminth infections and reduced allergy has yet to be proven [2], chemotherapeutic clearance of intestinal helminths can result in accentuated atopic responsiveness [11][12][13] and helminth infection blocks overt allergy in a number of animal models [14][15][16][17]. The degree to which helminths may influence allergy, however, is clearly variable between different parasite species [18], and is probably dependent upon the duration and intensity of infection [2,19], each factors that need to be taken into account in assessing this interaction.The concept that helminths may act in a beneficial way for therapy of immunological disorders is one that has been gaining * These author contributed equally to this work. Eur. J. Immunol. 20...

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Section: Discussionmentioning

confidence: 99%

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus

McSorley

O'Gorman

Blair³

et al. 2012

Eur J Immunol

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“…The role of DCs in inducing regulatory responses is illustrated by the action of schistosome lysophosphatidylserine, which acts on human DCs to promote IL-10-producing Tr1 cells (290), and the egg molecule -1, which drives murine DCs from mice to induce Foxp3 expression in T cells in vitro (316). In the H. polygyrus model, infection expands an unusual phenotype of CD11c low CD103 Ϫ DCs, which preferentially drive Foxp3 induction in naive T cells (165,258), while there is a loss of CD8␣ intermediate DCs that normally traffic from the epithelium to the draining lymph node (21).…”

Section: Dendritic Cellsmentioning

confidence: 99%

Helminth Infections and Host Immune Regulation

2012

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SUMMARY Helminth parasites infect almost one-third of the world's population, primarily in tropical regions. However, regions where helminth parasites are endemic record much lower prevalences of allergies and autoimmune diseases, suggesting that parasites may protect against immunopathological syndromes. Most helminth diseases are spectral in nature, with a large proportion of relatively asymptomatic cases and a subset of patients who develop severe pathologies. The maintenance of the asymptomatic state is now recognized as reflecting an immunoregulatory environment, which may be promoted by parasites, and involves multiple levels of host regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. Currently, there is much interest in whether helminth-associated immune regulation may ameliorate allergy and autoimmunity, with investigations in both laboratory models and human trials. Understanding and exploiting the interactions between these parasites and the host regulatory network are therefore likely to highlight new strategies to control both infectious and immunological diseases.

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“…Moreover, how helminth coinfection alters or suppresses the in vivo response of those relevant DC subsets to microbial agonists needs to be investigated. Two studies have demonstrated the emergence of a CD103 − CD11c lo DC population, distinct from plasmacytoid DCs, during chronic helminth infection 118,119 . CD11c lo DCs were ineffective stimulators of an effector response by CD4 + T cells and instead strongly drove expression of the transcription factor Foxp3 in naive CD4 + T cells, which resulted in the generation of T reg cells.…”

Section: Helminths Inhibit DC Activationmentioning

confidence: 99%

Effect of helminth-induced immunity on infections with microbial pathogens

2013

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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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The phenotype and function of naturally existing regulatory dendritic cells in nematode-infected mice

Cited by 22 publications

References 34 publications

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus

Helminth Infections and Host Immune Regulation

Effect of helminth-induced immunity on infections with microbial pathogens

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