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  1. Article ; Online: Networking between helminths, microbes, and mammals.

    Loke, P'ng / Harris, Nicola L

    Cell host & microbe

    2023  Volume 31, Issue 4, Page(s) 464–471

    Abstract: Just as mammals have coevolved with the intestinal bacterial communities that are part of the microbiota, intestinal helminths represent an important selective force on their mammalian host. The complex interaction between helminths, microbes, and their ... ...

    Abstract Just as mammals have coevolved with the intestinal bacterial communities that are part of the microbiota, intestinal helminths represent an important selective force on their mammalian host. The complex interaction between helminths, microbes, and their mammalian host is likely an important determinant of mutual fitness. The host immune system in particular is a critical interface with both helminths and the microbiota, and this crosstalk often determines the balance between tolerance and resistance against these widespread parasites. Hence, there are many examples of how both helminths and the microbiota can influence tissue homeostasis and homeostatic immunity. Understanding these processes at a cellular and molecular level is an exciting area of research that we seek to highlight in this review and that will potentially guide future treatment approaches.
    MeSH term(s) Animals ; Humans ; Helminths ; Helminthiasis ; Microbiota ; Immune Tolerance ; Host-Parasite Interactions ; Mammals
    Language English
    Publishing date 2023-04-13
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2023.02.008
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  2. Article ; Online: Redefining inflammatory macrophage phenotypes across stages and tissues by single-cell transcriptomics.

    Loke, P'ng / Lin, Jian-Da

    Science immunology

    2022  Volume 7, Issue 70, Page(s) eabo4652

    Abstract: Single-cell transcriptomic data identifies major activation paths of monocyte-derived macrophages as a framework for inflammatory tissue macrophages. ...

    Abstract Single-cell transcriptomic data identifies major activation paths of monocyte-derived macrophages as a framework for inflammatory tissue macrophages.
    MeSH term(s) Macrophages ; Phenotype ; Transcriptome
    Language English
    Publishing date 2022-04-15
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural ; Comment
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abo4652
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  3. Article ; Online: Recruitment and Maintenance of CX3CR1+CD4+ T Cells during Helminth Infection.

    Loredan, Denis G / Devlin, Joseph C / Khanna, Kamal M / Loke, P'ng

    Journal of immunology (Baltimore, Md. : 1950)

    2024  Volume 212, Issue 4, Page(s) 632–644

    Abstract: Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections. In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ ...

    Abstract Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections. In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni murine models of helminth infections, revealing CX3CR1+CD4+ T cells to be an activated tissue-homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA sequencing analysis of fate-mapped CX3CR1+CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+TCF-1+PD1+CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells resulted in fewer CX3CR1+CD4+ T cells during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance.
    MeSH term(s) Animals ; Mice ; CD4-Positive T-Lymphocytes/metabolism ; Helminthiasis/immunology ; Inflammation/metabolism ; Schistosoma mansoni/physiology
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2300451
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  4. Article ; Online: Helminth infections and cardiovascular diseases: A role for the microbiota and Mϕs?

    Lin, Jian-Da / Loke, P'ng

    Journal of leukocyte biology

    2021  Volume 110, Issue 6, Page(s) 1269–1276

    Abstract: Cardiovascular diseases are rising in developing countries with increasing urbanization and lifestyle changes and remains a major cause of death in the developed world. In this mini review, we discuss the possibility that the effect of helminth ... ...

    Abstract Cardiovascular diseases are rising in developing countries with increasing urbanization and lifestyle changes and remains a major cause of death in the developed world. In this mini review, we discuss the possibility that the effect of helminth infections on the immune system and the microbiota may affect risk factors in cardiovascular diseases such as atherosclerosis, as part of the hygiene hypothesis. The effects of Type 2 immune responses induced by helminths and helminth derived molecules on regulating metabolism and Mϕ function could be a mechanistic link for further investigation. We emphasize the complexity and difficulties in determining indirect or direct and causal relationships between helminth infection status and cardiovascular diseases. New experimental models, such as rewilding laboratory mice, whereby different aspects of the environment and host genetics can be carefully dissected may provide further mechanistic insights and therapeutic strategies for treating cardiovascular diseases.
    MeSH term(s) Animals ; Cardiovascular Diseases/immunology ; Helminthiasis/immunology ; Host-Parasite Interactions/immunology ; Humans ; Hygiene Hypothesis ; Macrophages/immunology ; Microbiota/immunology
    Language English
    Publishing date 2021-09-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1002/JLB.5MR0721-786R
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  5. Article ; Online: Effects of helminths on the human immune response and the microbiome.

    Loke, P'ng / Lee, Soo Ching / Oyesola, Oyebola O

    Mucosal immunology

    2022  Volume 15, Issue 6, Page(s) 1224–1233

    Abstract: Helminths have evolved sophisticated immune regulating mechanisms to prevent rejection by their mammalian host. Our understanding of how the human immune system responds to these parasites remains poor compared to mouse models of infection and this ... ...

    Abstract Helminths have evolved sophisticated immune regulating mechanisms to prevent rejection by their mammalian host. Our understanding of how the human immune system responds to these parasites remains poor compared to mouse models of infection and this limits our ability to develop vaccines as well as harness their unique properties as therapeutic strategies against inflammatory disorders. Here, we review how recent studies on human challenge infections, self-infected individuals, travelers, and endemic populations have improved our understanding of human type 2 immunity and its effects on the microbiome. The heterogeneity of responses between individuals and the limited access to tissue samples beyond the peripheral blood are challenges that limit human studies on helminths, but also provide opportunities to transform our understanding of human immunology. Organoids and single-cell sequencing are exciting new tools for immunological analysis that may aid this pursuit. Learning about the genetic and immunological basis of resistance, tolerance, and pathogenesis to helminth infections may thus uncover mechanisms that can be utilized for therapeutic purposes.
    MeSH term(s) Mice ; Animals ; Humans ; Helminths ; Helminthiasis ; Microbiota ; Immune Tolerance ; Immunity ; Host-Parasite Interactions ; Mammals
    Language English
    Publishing date 2022-06-22
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1038/s41385-022-00532-9
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  6. Article ; Online: The Influence of Genetic and Environmental Factors and Their Interactions on Immune Response to Helminth Infections.

    Oyesola, Oyebola O / Souza, Camila Oliveira Silva / Loke, P'ng

    Frontiers in immunology

    2022  Volume 13, Page(s) 869163

    Abstract: Helminth infection currently affect over 2 billion people worldwide, with those with the most pathologies and morbidities, living in regions with unequal and disproportionate access to effective healthcare solutions. Host genetics and environmental ... ...

    Abstract Helminth infection currently affect over 2 billion people worldwide, with those with the most pathologies and morbidities, living in regions with unequal and disproportionate access to effective healthcare solutions. Host genetics and environmental factors play critical roles in modulating and regulating immune responses following exposure to various pathogens and insults. However, the interplay of environment and genetic factors in influencing who gets infected and the establishment, persistence, and clearance of helminth parasites remains unclear. Inbred strains of mice have long been used to investigate the role of host genetic factors on pathogenesis and resistance to helminth infection in a laboratory setting. This review will discuss the use of ecological and environmental mouse models to study helminth infections and how this could be used in combination with host genetic variation to explore the relative contribution of these factors in influencing immune response to helminth infections. Improved understanding of interactions between genetics and the environment to helminth immune responses would be important for efforts to identify and develop new prophylactic and therapeutic options for the management of helminth infections and their pathogenesis.
    MeSH term(s) Animals ; Helminthiasis ; Helminths ; Host-Parasite Interactions/genetics ; Humans ; Immunity ; Mice ; Parasites
    Language English
    Publishing date 2022-04-29
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.869163
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  7. Article ; Online: Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth Infection.

    Harris, Nicola L / Loke, P'ng

    Immunity

    2018  Volume 48, Issue 2, Page(s) 396

    Language English
    Publishing date 2018-02-21
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2018.02.011
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  8. Article ; Online: Intestinal Macrophages in Resolving Inflammation.

    Hine, Ashley M / Loke, P'ng

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Volume 203, Issue 3, Page(s) 593–599

    Abstract: Macrophages not only regulate intestinal homeostasis by recognizing pathogens to control enteric infections but also employ negative feedback mechanisms to prevent chronic inflammation. Hence, macrophages are intriguing targets for immune-mediated ... ...

    Abstract Macrophages not only regulate intestinal homeostasis by recognizing pathogens to control enteric infections but also employ negative feedback mechanisms to prevent chronic inflammation. Hence, macrophages are intriguing targets for immune-mediated therapies, especially when barrier function in the gut is compromised to trigger aberrant inflammatory responses, most notably during inflammatory bowel diseases. Recently, there has been considerable progress in our understanding of human macrophage biology in different tissues, including the intestines. In this review, we discuss some new findings on the properties of distinct populations of intestinal macrophages, how resolution of inflammation and tissue repair by macrophages could be promoted by type 2 cytokines as well as other therapeutic interventions, and highlight some challenges for translating these findings into the future for this exciting area of immunology research.
    MeSH term(s) Bacterial Infections/immunology ; Cytokines/immunology ; Helminthiasis/immunology ; Humans ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/pathology ; Inflammatory Bowel Diseases/therapy ; Intestinal Mucosa/cytology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/pathology ; Macrophage Activation/immunology ; Macrophages/immunology
    Chemical Substances Cytokines
    Language English
    Publishing date 2019-05-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1900345
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  9. Article ; Online: Getting a Taste for Parasites in the Gut.

    Loke, P'ng / Cadwell, Ken

    Immunity

    2018  Volume 49, Issue 1, Page(s) 16–18

    Abstract: How type 2 immune responses are initiated is obscure. Nadjsombati et al. (2018), along with two other studies (Lei et al., 2018; Schneider et al., 2018), show that tuft cells can initiate type 2 responses by recognizing the metabolite succinate produced ... ...

    Abstract How type 2 immune responses are initiated is obscure. Nadjsombati et al. (2018), along with two other studies (Lei et al., 2018; Schneider et al., 2018), show that tuft cells can initiate type 2 responses by recognizing the metabolite succinate produced by intestinal parasites.
    MeSH term(s) Animals ; Diabetes Mellitus, Type 2 ; Intestines ; Parasites ; Succinic Acid ; Taste
    Chemical Substances Succinic Acid (AB6MNQ6J6L)
    Language English
    Publishing date 2018-07-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2018.07.002
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  10. Article ; Online: By CyTOF: Heterogeneity of Human Monocytes.

    Loke, P'ng / Niewold, Timothy B

    Arteriosclerosis, thrombosis, and vascular biology

    2017  Volume 37, Issue 8, Page(s) 1423–1424

    MeSH term(s) Dendritic Cells ; Humans ; Macrophages ; Monocytes
    Language English
    Publishing date 2017-07-26
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.117.309645
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