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1.
Parasite Immunol ; 40(2)2018 02.
Article in English | MEDLINE | ID: mdl-28369954

ABSTRACT

Hookworm is a major public health concern, yet still relatively little is known about the immunological responses involved in human infection. Animal studies are mainly confined to using the natural rodent helminth Nippostrongylus brasiliensis as this has been proposed as the most accurate model of hookworm infection in the mouse, with both its life cycle and the immune responses it invokes having been extremely well characterized. In this review, we examine the roles that type 2 innate lymphoid cells (ILC2s) play in immunity and host tolerance to hookworm infection, particularly N. brasiliensis. This includes their role in the initiation and regulation of immune responses, as well as in the resolution and limitation of tissue damage required after an infection with a large organism, such as a helminth.


Subject(s)
Ancylostomatoidea/immunology , Cytokines/immunology , Hookworm Infections/immunology , Immunity, Innate/immunology , Nippostrongylus/immunology , Th2 Cells/immunology , Animals , Disease Models, Animal , Female , Hookworm Infections/parasitology , Humans , Male , Mice , Neglected Diseases/immunology , Neglected Diseases/parasitology
2.
Curr Protoc Mouse Biol ; 7(4): 236-286, 2017 Dec 20.
Article in English | MEDLINE | ID: mdl-29261231

ABSTRACT

Hookworm infections (Necator americanus or Ancylostoma duodenale) represent a major neglected tropical disease, affecting approximately 700 million people worldwide, and can cause severe morbidity due to the need for these worms to feed on host blood. N. brasiliensis and H. polygrus, both rodent parasites, are the two most commonly employed laboratory models of experimental hookworm infection. Both parasites evoke type 2 immune responses, and their use has been instrumental in generating fundamental insight into the molecular mechanisms of type-2 immunity and for understanding how the immune response can control parasite numbers. Here we provide a complete set of methods by which to investigate the natural progression of infection and the host immunological responses in the lung and intestine of H. polygyrus- and N. brasiliensis-infected mice. Detailed information is included about the most important parasitological and immunological measurements to perform at each time point. © 2017 by John Wiley & Sons, Inc.


Subject(s)
Disease Models, Animal , Immunity, Humoral , Mice , Nematospiroides dubius/physiology , Nippostrongylus/physiology , Strongylida Infections/immunology , Animals , Disease Progression
3.
Mucosal Immunol ; 9(2): 428-43, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26286232

ABSTRACT

Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.


Subject(s)
Immunity, Mucosal/drug effects , Macrophages/immunology , Nematospiroides dubius/immunology , Strongylida Infections/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Antibodies, Neutralizing/pharmacology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/immunology , Female , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/immunology , Gene Expression Regulation , Granulocytes/drug effects , Granulocytes/immunology , Granulocytes/parasitology , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-2/pharmacology , Interleukin-2 Receptor alpha Subunit/antagonists & inhibitors , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Macrophages/drug effects , Macrophages/parasitology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Nematospiroides dubius/drug effects , Parasite Load , Signal Transduction , Strongylida Infections/drug therapy , Strongylida Infections/parasitology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/parasitology , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/parasitology , Th17 Cells/drug effects , Th17 Cells/immunology , Th17 Cells/parasitology , Transcription Factors/genetics , Transcription Factors/immunology
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