ArticleBMC biology2005
Heterologous expression of the filarial nematode alt gene products reveals their potential to inhibit immune function.
Article in BMC biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Modulation of the Immune Response by Nematode Derived Molecules.International journal of molecular sciences · 2025Review
- Unraveling the Dynamics of Human Filarial Infections: Immunological Responses, Host Manifestations, and Pathogen Biology.Pathogens (Basel, Switzerland) · 2025Review
- The Immune Response to Nematode Infection.International journal of molecular sciences · 2023Review
- Harnessing Immune Evasion Strategy of Lymphatic Filariae: A Therapeutic Approach against Inflammatory and Infective Pathology.Vaccines · 2022Review
- The Functional Parasitic Worm Secretome: Mapping the Place ofPathogens (Basel, Switzerland) · 2020Review
- Immunological evaluation of fusion protein ofParasite epidemiology and control · 2019Article
- Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules.Immunity · 2018Review
- Parasites as negative regulators of cancer.Bioscience reports · 2018Review
- Elucidation of immunological response and its regulatory network by P-TUFT-ALT-2: a promising fusion protein vaccine for human lymphatic filariasis.Royal Society open science · 2018Article
- Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles.Frontiers in immunology · 2018Review
- Helminths in the gastrointestinal tract as modulators of immunity and pathology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes.Indian journal of clinical biochemistry : IJCB · 2017Article
- Modulation of the Immune Response by Nematode Secreted Acetylcholinesterase Revealed by Heterologous Expression in Trypanosoma musculi.PLoS pathogens · 2016Article
- Host parasite communications-Messages from helminths for the immune system: Parasite communication and cell-cell interactions.Molecular and biochemical parasitology · 2016Review
- Brugia pahangi: immunization with early L3 ES alters parasite migration, and reduces microfilaremia and lymphatic lesion formation in gerbils (Meriones unguiculatus).Experimental parasitology · 2013Article
- Protective immune responses to biolistic DNA vaccination of Brugia malayi abundant larval transcript-2.Vaccine · 2012Article
- Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes.PLoS neglected tropical diseases · 2012Article
- Modulation of specific and allergy-related immune responses by helminths.Journal of biomedicine & biotechnology · 2011Review
- daf-7-related TGF-beta homologues from Trichostrongyloid nematodes show contrasting life-cycle expression patterns.Parasitology · 2010Article
- Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity.Molecular and biochemical parasitology · 2009Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundParasites exploit sophisticated strategies to evade host immunity that require both adaptation of existing genes and evolution of new gene families. We have addressed this question by testing the immunological function of novel genes from helminth parasites, in which conventional transgenesis is not yet possible. We investigated two such novel genes from Brugia malayi termed abundant larval transcript (alt), expression of which reaches ~5% of total transcript at the time parasites enter the human host.
resultsTo test the hypothesis that ALT proteins modulate host immunity, we adopted an alternative transfection strategy to express these products in the protozoan parasite Leishmania mexicana. We then followed the course of infection in vitro in macrophages and in vivo in mice. Expression of ALT proteins, but not a truncated mutant, conferred greater infectivity of macrophages in vitro, reaching 3-fold higher parasite densities. alt-transfected parasites also caused accelerated disease in vivo, and fewer mice were able to clear infection of organisms expressing ALT. alt-transfected parasites were more resistant to IFN-gamma-induced killing by macrophages. Expression profiling of macrophages infected with transgenic L. mexicana revealed consistently higher levels of GATA-3 and SOCS-1 transcripts, both associated with the Th2-type response observed in in vivo filarial infection.
conclusionLeishmania transfection is a tractable and informative approach to determining immunological functions of single genes from heterologous organisms. In the case of the filarial ALT proteins, our data suggest that they may participate in the Th2 bias observed in the response to parasite infection by modulating cytokine-induced signalling within immune system cells.
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