Proinflammatory cytokines dominate the early immune response to filarial parasites

Babu, Subash; Nutman, Thomas B

doi:10.4049/jimmunol.171.12.6723

Cited by 78Parasitic Diseases Research and TreatmentParasites and Host InteractionsHelminth infection and control

Proinflammatory cytokines dominate the early immune response to filarial parasites

Babu, Subash, Nutman, Thomas B·2003·The Journal of Immunology

DOI 10.4049/jimmunol.171.12.6723

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Abstract

Although the early human immune response to the infective-stage larvae (L3) of Brugia malayi has not been well-characterized in vivo (because of the inability to determine the precise time of infection), the consensus has been that it must involve a predominant Th2 environment. We have set up an in vitro system to study this early immune response by culturing PBMC from unexposed individuals with live L3 of B. malayi. After 24 h of culture, T cell responses were examined by flow cytometry and by quantitative real-time RT-PCR for multiple cytokines. T cells were activated early following exposure to L3 as indicated by up-regulation of surface markers CD69 and CD71. The frequency of T cells expressing proinflammatory Th1 cytokines (IFN-gamma, TNF-alpha, GM-CSF, IL-1alpha, and IL-8) but not Th2 cytokines (IL-4, IL-5, IL-6, IL-10, and IL-13) was significantly increased in response to L3. This T cell response occurred in both the CD4 and CD8 T cell compartment and was restricted to the effector/memory pool (CD45RO(+)). This T cell response was not due to LPS activity from the parasite or from its endosymbiont, Wolbachia; moreover, it required the presence of APC as well as direct contact with live L3. Real-time RT-PCR analysis of multiple cytokines in the T cells confirmed the increased expression of proinflammatory Th1 cytokines. Up-regulation of these cytokines suggests that the primary immune response to the live infective stage of the parasite is not predominantly Th2 in nature but rather dominated by a proinflammatory response.

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Helminth infections are usually associated with polarised Th2/Th1 immune responses.
“Helminths infections are usually associated with polarised Th2/Th1 immune responses [16,57].”
From Emergent and Neglected Equine Filariosis in Egypt: Species Diversity and Host Immune Response (2022) · cites this paper as [57]
Early filarial infection is accompanied by elevation of Th1 over Th2 cytokines.
“Subash and Nutman [57] reported that early filarial infection was accompanied by the elevation of Th1 over Th2 cytokines, which is essential to understanding the pathogenesis of infection and the host–parasite relationships.”
From Emergent and Neglected Equine Filariosis in Egypt: Species Diversity and Host Immune Response (2022) · cites this paper as Subash and Nutman [57]

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Authors: Babu, S., & Nutman, T. B.
Affiliations: National Institutes of Health (US)
ORCID: Babu, Subash
Nutman, Thomas B
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2003-12
Volume: 171
Issue: 12
Pages: 6723-6732
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.171.12.6723
OpenAlex: W2166067725
Cited by: 78
References: 39
Citations by year: 2025: 3 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 4
FWCI: 3.11
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
Health Sciences › Veterinary › Small Animals › Helminth infection and control
Keywords: Brugia malayi, filariasis, infective larvae, Th1 response, inflammatory cytokines, Th2 immune response, T cell activation, CD69, transferrin receptor, CD45RO+ memory T cells, CD4 and CD8 T cells, antigen-presenting cells, Wolbachia, interferon-gamma, TNF-α, GM-CSF, IL-1α, interleukin-8
MeSH terms: Animals, Antigen-Presenting Cells, Antigens, Helminth, Cell Communication, Cells, Cultured, Flow Cytometry, Host-Parasite Interactions, Humans, Lipopolysaccharides, Lymphocyte Activation, T-Lymphocytes, CD4-Positive T-Lymphocytes, Cytokines, Brugia malayi, CD8-Positive T-Lymphocytes, Th1 Cells, Inflammation Mediators, Reverse Transcriptase Polymerase Chain Reaction

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Proinflammatory cytokines dominate the early immune response to filarial parasites

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